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Sample records for sustain pulsatile gnrh

  1. Pulsatile GnRH Is Superior to hCG in Therapeutic Efficacy in Adolescent Boys With Hypogonadotropic Hypogonadodism.

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    Gong, Chunxiu; Liu, Ying; Qin, Miao; Wu, Di; Wang, Xiaoling

    2015-07-01

    We investigated the efficacy and safety of two different treatments that have not been evaluated in peripuberty boys with hypogonadotropic hypogonadism (HH). The objective of the study was to assess the effectiveness and safety of GnRH or human chorionic gonadotropin (hCG) treatment in adolescent boys with HH. Twelve patients received 8-10 μg of GnRH, sc injected every 90 minutes using a pump. Another 22 patients received hCG, injected im as follows: for the first 3 months, 1000 IU of hCG was injected two times per week and then once every other day for the next 3 months. The dose of hCG was increased to 2000 IU after a 6-month treatment and the above cycle was repeated for another 6 months. All patients were treated for 12-14 months and followed up every 3 months. Thirty-five participants were chosen from Beijing Children's Hospital from 2008 to 2014. Twenty-three patients with Kallmann syndrome and 12 with normosmic idiopathic hypogonadotropic hypogonadism. The age ranged from 10 to 16 years. Twelve patients were treated with pulsatile pump GnRH (group 1), and 22 patients were treated with im hCG (group 2). One patient was treated successively with hCG and GnRH, which was removed in data analysis. Testicular volume was measured by an orchidometer. The levels of T, LH, and FSH serum were measured with a chemiluminesent immunoassay. Bone age was measured by x-ray. Patients treated with GnRH showed larger testes than those treated with hCG. Patients in both groups showed a significantly increased length of penis and T levels. But the difference of the two groups was not statistically significant. There was no significant difference in side effects in both groups. Boys with HH may be effectively treated with GnRH. We suggested that GnRH exhibits higher efficacy in treating adolescent boys with HH than hCG.

  2. A mathematical model for LH release in response to continuous and pulsatile exposure of gonadotrophs to GnRH

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    Reed Michael C

    2004-09-01

    Full Text Available Abstract In a previous study, a model was developed to investigate the release of luteinizing hormone (LH from pituitary cells in response to a short pulse of gonadotropin-releasing hormone (GnRH. The model included: binding of GnRH to its receptor (R, dimerization and internalization of the hormone receptor complex, interaction with a G protein, production of inositol 1,4,5-trisphosphate (IP3, release of calcium from the endoplasmic reticulum (ER, entrance of calcium into the cytosol via voltage gated membrane channels, pumping of calcium out of the cytosol via membrane and ER pumps, and release of LH. The extended model, presented in this paper, also includes the following physiologically important phenomena: desensitization of calcium channels; internalization of the dimerized receptors and recycling of some of the internalized receptors; an increase in Gq concentration near the plasma membrane in response to receptor dimerization; and basal rates of synthesis and degradation of the receptors. With suitable choices of the parameters, good agreement with a variety of experimental data of the LH release pattern in response to pulses of various durations, repetition rates, and concentrations of GnRH were obtained. The mathematical model allows us to assess the effects of internalization and desensitization on the shapes and time courses of LH response curves.

  3. Pulsatile Hyperglycaemia Induces Vascular Oxidative Stress and GLUT 1 Expression More Potently than Sustained Hyperglycaemia in Rats on High Fat Diet

    DEFF Research Database (Denmark)

    Rakipovski, Gunaj; Lykkesfeldt, Jens; Raun, Kirsten

    2016-01-01

    expression of glucose transporter 1 (GLUT1), gp-91(PHOX) and super oxide dismutase (SOD), while only the PLG group showed increased accumulation of oxidative stress and oxidised low density lipoprotein (oxLDL) in aorta. Conclusion Pulsatile hyperglycaemia induced relatively higher levels of oxidative stress...... systemically and in aorta in particular than overt sustained hyperglycaemia thus supporting the clinical observations that pulsatile hyperglycaemia is an independent risk factor for diabetes related macrovascular complications....

  4. Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome

    NARCIS (Netherlands)

    Bayram, N.; van Wely, M.; van der Veen, F.

    2004-01-01

    BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in

  5. Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome

    NARCIS (Netherlands)

    Bayram, N.; van Wely, M.; Vandekerckhove, P.; Lilford, R.; van der Veen, F.

    2000-01-01

    BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in

  6. Physiology of the gonadotrophin-releasing hormone (GnRH) neurone: studies from embryonic GnRH neurones.

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    Constantin, S

    2011-06-01

    Gonadotrophin-releasing hormone (GnRH)-secreting neurones are the final output of the central nervous system driving fertility in all mammals. Although it has been known for decades that the efficiency of communication between the hypothalamus and the pituitary depends on the pulsatile profile of GnRH secretion, how GnRH neuronal activity is patterned to generate pulses at the median eminence is unknown. To date, the scattered distribution of the GnRH cell bodies remains the main limitation to assessing the cellular events that could lead to pulsatile GnRH secretion. Taking advantage of the unique developmental feature of GnRH neurones, the nasal explant model allows primary GnRH neurones to be maintained within a micro-network where pulsatile secretion is preserved and where individual cellular activity can be monitored simultaneously across the cell population. This review summarises the data obtained from work using this in vitro model, and brings some insights into GnRH cellular physiology. © 2011 The Author. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  7. The GnRH Pulse Generator

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    Pasha Grachev

    2016-12-01

    Full Text Available The pulsatile secretion of hormones is an efficient way of coding a large variety of chemical messages. The GnRH pulse pattern determines which gonadotropin is released when and at what concentration, prescribing a detailed set of instructions to the gonads that produce changes in the steroid hormone milieu. Although GnRH neurons possess some inherent rhythmicity, they are diffusely situated within the hypothalamus and in isolation are only capable of generating physiologically irrelevant messages, hence a synchronization module exists upstream. The identity of the neural unit comprising the GnRH pulse generator is now generally thought to include KNDy neurons in the arcuate nucleus. These neurons coexpress the neuropeptides kisspeptin, neurokinin B and dynorphin A, as well as other transmitters, and are in intimate contact with the GnRH network. The GnRH pulse generator’s function is the precise control of GnRH neuron excitability, coordinated activation, stimulation of neurosecretory events, modulation of gene transcription and the mediation of the negative feedback effect of gonadal steroids. Additionally, the GnRH pulse generator is an ideal venue for the integration of various sensory and homeostatic cues that regulate reproductive functions. In this chapter we provide a historical perspective of the elegant science that sparked interest in the central mechanisms underlying the functions of the reproductive system, explain how hypotheses surrounding GnRH pulse generation have evolved and describe the current state of knowledge within the dynamic field of GnRH pulse generator research.

  8. The GnRH receptor and the response of gonadotrope cells to GnRH pulse frequency code. A story of an atypical adaptation of cell function relying on a lack of receptor homologous desensitization.

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    Christian Bleux

    2010-01-01

    Full Text Available Brain control of the reproductive system is mediated through hypothalamic gonadotropin-releasing hormone (GnRH which activates specific receptors (GnRHR present at the surface of the pituitary gonadotropes to trigger secretion of the two gonadotropins LH and FSH. A unique feature of this system is the high dependence on the secretion mode of GnRH, which is basically pulsatile but undergoes considerable fluctuations in pulse frequency pattern in response to endogenous or external factors. How the physiological fluctuations of GnRH secretion that orchestrate normal reproduction are decoded by the gonadotrope cell machinery to ultimately control gonadotropin release and/or subunit gene transcription has been the subject of intensive studies during the past decades. Surprisingly, the mammalian GnRHR is unique among G protein-coupled receptor family as it lacks the carboxy-terminal tail usually involved in classical endocytotic process. Accordingly, it does not desensitize properly and internalizes very poorly. Both this atypical intrinsic property and post-receptor events may thus contribute to decode the GnRH signal. This includes the participation of a network of signaling pathways that differently respond to GnRH together with a growing amount of genes differentially sensitive to pulse frequency. Among these are two pairs of genes, the transcription factors EGR-1 and NAB, and the regulatory factors activin and follistatin, that function as intracellular autoregulatory feedback loops controlling respectively LHbeta and FSHbeta gene expression and hence, LH and FSH synthesis. Pituitary gonadotropes thus represent a unique model of cells functionally adapted to respond to a considerably fluctuating neuroendocrine stimulation, from short individual pulses to sustained GnRH as observed at the proestrus of ovarian cycle. Altogether, the data emphasize the adaptative reciprocal complementarity of hypothalamic GnRH neurones and pituitary gonadotropes to

  9. Changes in peripheral blood levels and pulse frequencies of GnRH in patients with hypopituitarism.

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    Hayashi, M; Takanashi, N; Yaoi, Y

    1998-09-01

    Pituitary dysfunction occasionally results from brain tumors or the surgical resection of brain tumors. The authors examined two patients with hypogonadotropic secondary amenorrhea, who had undergone surgical removal of brain tumors. Changes in immunoreactive gonadotropin-releasing hormone (GnRH) secretion are of interest in patients with a gonadotropin and gonadal steroid deficit, because both steroid and pituitary feedback systems are altered by tumors or tumor resection. The authors thus measured GnRH, luteinizing hormone, and follicle-stimulating hormone levels every 15 minutes for 4 hours by radioimmunoassay and investigated qualitative and quantitative changes in the pulsatile patterns of these hormones in two hypogonadotropic hypogonadism patients. They also performed similar multiple measurements of GnRH in two normal cycle women in follicular phase and two postmenopausal women. The concentration of plasma GnRH in two hypopituitarism patients was compared with that in two normal cycle women and two postmenopausal women. The study showed that the peripheral blood level of GnRH was significantly lower in two hypopituitarism patients than in both normal cycle and postmenopausal women, and that the pulsatile frequency was not different among these three groups. These findings suggest that alteration of feedback systems results in a decrease in the blood level of GnRH, and that pulses of GnRH maintain normal fluctuation despite the alteration of the hormonal circumstances in two hypogonadotropic hypogonadism patients.

  10. Regulation of intracellular signaling cascades by GNRH pulse frequency in the rat pituitary: roles for CaMK II, ERK, and JNK activation.

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    Burger, Laura L; Haisenleder, Daniel J; Aylor, Kevin W; Marshall, John C

    2008-11-01

    Pulsatile GnRH (GNRH) differentially regulates LH and FSH subunit genes, with faster frequencies favoring Lhb transcription and slower favoring Fshb. Various intracellular pathways mediate the effects of GNRH, including CaMK II (CAMK2), ERK, and JNK. We examined whether activation of these pathways is regulated by GNRH pulse frequency in vivo. GNRH-deficient rats received GNRH pulses (25 ng i.v. every 30 or 240 min for 8 h, vehicle to controls). Pituitaries were collected 5 min after the last pulse, bisected, and one half processed for RNA (to measure beta subunit primary transcripts [PTs]) and the other for protein. Phosphorylated CAMK2 (phospho-CAMK2), ERK (mitogen-activated protein kinase 1/3 [MAPK1/3], also known as p42 ERK2 and p44 ERK1, respectively), and JNK (MAPK8/9, also known as p46 JNK1 and p54 JNK2, respectively) were determined by Western blotting. The 30-min pulses maximally stimulated Lhb PT (8-fold), whereas 240 min was optimal for Fshb PT (3-fold increase). Both GNRH pulse frequencies increased phospho-CAMK2 4-fold. Activation of MAPK1/3 was stimulated by both 30- and 240-min pulses, but phosphorylation of MAPK3 was significantly greater following slower GNRH pulses (240 min: 4-fold, 30 min: 2-fold). MAPK8/9 activation was unchanged by pulsatile GNRH in this paradigm, but as previous results showed that GNRH-induced activation of MAPK8/9 is delayed, 5 min after GNRH may not be optimal to observe MAPK8/9 activation. These data show that CAMK2 is activated by GNRH, but not in a frequency-dependant manner, whereas MAPK3 is maximally stimulated by slow-frequency GNRH pulses. Thus, the ERK response to slow pulse frequency is part of the mechanisms mediating Fhb transcriptional responses to GNRH.

  11. Regulation of Intracellular Signaling Cascades by GNRH Pulse Frequency in the Rat Pituitary: Roles for CaMK II, ERK, and JNK Activation1

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    Burger, Laura L.; Haisenleder, Daniel J.; Aylor, Kevin W.; Marshall, John C.

    2008-01-01

    Pulsatile GnRH (GNRH) differentially regulates LH and FSH subunit genes, with faster frequencies favoring Lhb transcription and slower favoring Fshb. Various intracellular pathways mediate the effects of GNRH, including CaMK II (CAMK2), ERK, and JNK. We examined whether activation of these pathways is regulated by GNRH pulse frequency in vivo. GNRH-deficient rats received GNRH pulses (25 ng i.v. every 30 or 240 min for 8 h, vehicle to controls). Pituitaries were collected 5 min after the last pulse, bisected, and one half processed for RNA (to measure beta subunit primary transcripts [PTs]) and the other for protein. Phosphorylated CAMK2 (phospho-CAMK2), ERK (mitogen-activated protein kinase 1/3 [MAPK1/3], also known as p42 ERK2 and p44 ERK1, respectively), and JNK (MAPK8/9, also known as p46 JNK1 and p54 JNK2, respectively) were determined by Western blotting. The 30-min pulses maximally stimulated Lhb PT (8-fold), whereas 240 min was optimal for Fshb PT (3-fold increase). Both GNRH pulse frequencies increased phospho-CAMK2 4-fold. Activation of MAPK1/3 was stimulated by both 30- and 240-min pulses, but phosphorylation of MAPK3 was significantly greater following slower GNRH pulses (240 min: 4-fold, 30 min: 2-fold). MAPK8/9 activation was unchanged by pulsatile GNRH in this paradigm, but as previous results showed that GNRH-induced activation of MAPK8/9 is delayed, 5 min after GNRH may not be optimal to observe MAPK8/9 activation. These data show that CAMK2 is activated by GNRH, but not in a frequency-dependant manner, whereas MAPK3 is maximally stimulated by slow-frequency GNRH pulses. Thus, the ERK response to slow pulse frequency is part of the mechanisms mediating Fhb transcriptional responses to GNRH.. PMID:18716286

  12. Imaging in pulsatile tinnitus

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    Madani, G. [Radiology Department, St Mary' s Hospital, London (United Kingdom)], E-mail: gittamadani@yahoo.com; Connor, S.E.J. [Neuroradiology Department, King' s College Hospital, London (United Kingdom)

    2009-03-15

    Tinnitus may be continuous or pulsatile. Vascular lesions are the most frequent radiologically demonstrable cause of pulsatile tinnitus. These include congenital vascular anomalies (which may be arterial or venous), vascular tumours, and a variety of acquired vasculopathies. The choice of imaging depends on the clinical findings. If a mass is present at otoscopy, thin-section computed tomography (CT) is indicated. In the otoscopically normal patient, there is a range of possible imaging approaches. However, combined CT angiography and venography is particularly useful.

  13. EFFECT OF INVIVO PRETREATMENT WITH ESTRADIOL AND EITHER GNRH, GNRH AGONISTIC ANALOG OR GNRH ANTAGONISTIC ANALOG ON GNRH-STIMULATED SECRETION OF LH INVITRO

    NARCIS (Netherlands)

    SCHUILING, GA; KOITER, TR; MOES, H

    1991-01-01

    In vivo treatment with GnRH or with GnRH agonistic analog (AG), but not with GnRH antagonistic analog (ANT), depleted the LH stores of the rat pituitary gland. This depletion was potentiated by oestradiol. Oestradiol augmented the in vitro LH response of the pituitary gland to GnRH. This augmenting

  14. Kisspeptin Can Stimulate Gonadotropin-Releasing Hormone (GnRH) Release by a Direct Action at GnRH Nerve Terminals

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    d'Anglemont de Tassigny, Xavier; Fagg, Lisa A.; Carlton, Mark B. L.; Colledge, William H.

    2008-01-01

    The G protein-coupled receptor GPR54, and its peptide ligand kisspeptin (Kp), are crucial for the induction and maintenance of mammalian reproductive function. GPR54 is expressed by GnRH neurons and is directly activated by Kp to stimulate GnRH release. We hypothesized that Kp may be able to act at the GnRH nerve terminals located in the mediobasal hypothalamus (MBH) region. To test this hypothesis, we used organotypic culture of MBH explants challenged with Kp, followed by RIA to detect GnRH released into the cultured medium. Kp stimulation for 1 h induced GnRH release from wild-type male MBH in a dose-dependent manner, whereas this did not occur in MBH explants isolated from Gpr54 null mice. Continuous Kp stimulation caused a sustained GnRH release for 4 h, followed by a decrease of GnRH release, suggesting a desensitization of GPR54 activity. Tetrodotoxin did not alter the Kp-induced GnRH release, indicating that Kp can act directly at the GnRH nerve terminals. To localize Gpr54 expression within the MBH, we used transgenic mice, in which Gpr54 expression is tagged with an IRES-LacZ reporter gene and can be visualized by β-galactosidase staining. Gpr54 expression was detected outside of the median eminence, in the pars tuberalis. In conclusion, our results provide evidence for a potent stimulating effect of Kp at GnRH nerve terminals in the MBH of the mouse. This study suggests a new point at which Kp can act on GnRH neurons. PMID:18450966

  15. Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human

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    Erik eHrabovszky

    2013-09-01

    Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.

  16. Orexin-A suppresses the pulsatile secretion of luteinizing hormone via beta-endorphin.

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    Irahara, M; Tamura, T; Matuzaki, T; Saito, S; Yasui, T; Yamano, S; Kamada, M; Aono, T

    2001-02-16

    Orexins, the novel hypothalamic neuropeptides that stimulate feeding behavior, have been shown to suppress the pulsatile secretion of LH in ovariectomized rats. However, the mechanism of this action is still not clear. We examined the effect of naloxone, a specific opioid antagonist, on the suppression of the pulsatile secretion of LH by orexins to determine whether beta-endorphin is involved in this suppressive effect. We administered orexins intracerebroventricularly and injected naloxone intravenously in ovariectomized rats, and we measured the serum LH concentration to analyze the pulsatile secretion. Administration of orexin-A significantly reduced the mean LH concentration and the pulse frequency, but coadministration of naloxone significantly restored the mean LH concentration and the pulse frequency. Administration of orexin-B also significantly reduced the mean LH concentration and the pulse frequency, and coadministration of naloxone did not restore them. These results indicate that orexin-A, but not orexin-B, suppresses GnRH secretion via beta-endorphin.

  17. Hedgehog-PKA signaling and gnrh3 regulate the development of zebrafish gnrh3 neurons.

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    Ming-Wei Kuo

    Full Text Available GnRH neurons secrete GnRH that controls the development of the reproduction system. Despite many studies, the signals controlling the development of GnRH neurons from its progenitors have not been fully established. To understand the development of GnRH neurons, we examined the development of gnrh3-expressing cells using a transgenic zebrafish line that expresses green fluorescent protein (GFP and LacZ driven by the gnrh3 promoter. GFP and LacZ expression recapitulated that of gnrh3 in the olfactory region, olfactory bulb and telencephalon. Depletion of gnrh3 by morpholinos led to a reduction of GFP- and gnrh3-expressing cells, while over-expression of gnrh3 mRNA increased the number of these cells. This result indicates a positive feed-forward regulation of gnrh3 cells by gnrh3. The gnrh3 cells were absent in embryos that lack Hedgehog signaling, but their numbers were increased in embryos overexpressing shhb. We manipulated the amounts of kinase that antagonizes the Hedgehog signaling pathway, protein kinase A (PKA, by treating embryos with PKA activator forskolin or by injecting mRNAs encoding its constitutively active catalytic subunit (PKA* and dominant negative regulatory subunit (PKI into zebrafish embryos. PKA* misexpression or forskolin treatment decreased GFP cell numbers, while PKI misexpression led to ectopic production of GFP cells. Our data indicate that the Hedgehog-PKA pathway participates in the development of gnrh3-expressing neurons during embryogenesis.

  18. Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54.

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    Jayasena, Channa N; Abbara, Ali; Veldhuis, Johannes D; Comninos, Alexander N; Ratnasabapathy, Risheka; De Silva, Akila; Nijher, Gurjinder M K; Ganiyu-Dada, Zainab; Mehta, Amrish; Todd, Catriona; Ghatei, Mohammad A; Bloom, Stephen R; Dhillo, Waljit S

    2014-06-01

    Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6 ± 0.4, vehicle; 5.0 ± 0.5, kisspeptin-54, P 54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P 54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.

  19. Surface obstacles in pulsatile flow

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    Carr, Ian A.; Plesniak, Michael W.

    2016-11-01

    Flows past obstacles mounted on flat surfaces have been widely studied due to their ubiquity in nature and engineering. For nearly all of these studies, the freestream flow over the obstacle was steady, i.e. constant velocity unidirectional flow. Unsteady, pulsatile flows occur frequently in biology, geophysics, biomedical engineering, etc. Our study is aimed at extending the comprehensive knowledge base that exists for steady flows to considerably more complex pulsatile flows. Beyond the important practical applications, characterizing the vortex and wake dynamics of flows around surface obstacles embedded in pulsatile flows can provide insights into the underlying physics in all wake and junction flows. In this study, we experimentally investigated the wake of four canonical surface obstacles: hemisphere, cube, and circular cylinders with aspect ratio of 1:1 and 2:1. Phase-averaged PIV and hot-wire anemometry are used to characterize the dynamics of coherent structures in the wake and at the windward junction of the obstacles. Complex physics occur during the deceleration phase of the pulsatile inflow. We propose a framework for understanding these physics based on self-induced vortex propagation, similar to the phenomena exhibited by vortex rings. This material is based in part upon work supported by the National Science Foundation under Grant Number CBET-1236351, and GW Centeor Biomimetics and Bioinspired Engineering (COBRE).

  20. Clinical outcomes of pulsatile and non-pulsatile mode of perfusion.

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    Haines, Nikkole; Wang, Shigang; Undar, Akif; Alkan, Tijen; Akcevin, Atif

    2009-03-01

    A longstanding debate remains over whether or not pulsatile flow provides better perfusion during cardiopulmonary bypass (CPB). This paper provides a guide for clinical investigation, as well as current laboratory and clinical evidence concerning pulsatile and non-pulsatile perfusion. This evidence is in the form of in vitro and in vivo experiments and clinical trials. We review the literature and provide personal experience from the Pediatric Cardiac Research Laboratories at the Penn State Hershey Children's Hospital. Pulsatility is emerging as the preferred perfusion method for CPB. Clinical evidence show better cardiac, renal, and pulmonary outcomes in patients receiving pulsatile perfusion. Furthermore, better cytokine, endothelin, and hormone levels and a higher respiratory index are shown in pulsatile perfusion modes compared with non-pulsatile perfusion modes. In recent years, evidence has amounted that supports a shift toward pulsatility in these procedures over non-pulsatility. Currently, more evaluation of circuit components and patient outcomes is needed.

  1. Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat.

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    Xiao-Feng Li

    2009-12-01

    Full Text Available Kisspeptin and its G protein-coupled receptor (GPR 54 are essential for activation of the hypothalamo-pituitary-gonadal axis. In the rat, the kisspeptin neurons critical for gonadotropin secretion are located in the hypothalamic arcuate (ARC and anteroventral periventricular (AVPV nuclei. As the ARC is known to be the site of the gonadotropin-releasing hormone (GnRH pulse generator we explored whether kisspeptin-GPR54 signalling in the ARC regulates GnRH pulses.We examined the effects of kisspeptin-10 or a selective kisspeptin antagonist administration intra-ARC or intra-medial preoptic area (mPOA, (which includes the AVPV, on pulsatile luteinizing hormone (LH secretion in the rat. Ovariectomized rats with subcutaneous 17beta-estradiol capsules were chronically implanted with bilateral intra-ARC or intra-mPOA cannulae, or intra-cerebroventricular (icv cannulae and intravenous catheters. Blood samples were collected every 5 min for 5-8 h for LH measurement. After 2 h of control blood sampling, kisspeptin-10 or kisspeptin antagonist was administered via pre-implanted cannulae. Intranuclear administration of kisspeptin-10 resulted in a dose-dependent increase in circulating levels of LH lasting approximately 1 h, before recovering to a normal pulsatile pattern of circulating LH. Both icv and intra-ARC administration of kisspeptin antagonist suppressed LH pulse frequency profoundly. However, intra-mPOA administration of kisspeptin antagonist did not affect pulsatile LH secretion.These data are the first to identify the arcuate nucleus as a key site for kisspeptin modulation of LH pulse frequency, supporting the notion that kisspeptin-GPR54 signalling in this region of the mediobasal hypothalamus is a critical neural component of the hypothalamic GnRH pulse generator.

  2. A single injection of kisspeptin-54 temporarily increases luteinizing hormone pulsatility in healthy women.

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    Jayasena, C N; Comninos, A N; Veldhuis, J D; Misra, S; Abbara, A; Izzi-Engbeaya, C; Donaldson, M; Ghatei, M A; Bloom, S R; Dhillo, W S

    2013-10-01

    Kisspeptin is a novel hypothalamic peptide which stimulates endogenous gonadotrophin releasing hormone (GnRH) secretion. A single subcutaneous bolus injection of kisspeptin-54 increases circulating luteinizing hormone (LH) levels in women, but its acute effects on LH pulsatility are not known. To investigate the effects of a single subcutaneous (sc) injection of kisspeptin-54 administration on LH pulsatility in healthy female volunteers. Six healthy female adult volunteers underwent 10-minute blood sampling for serum LH measurement for 8 h during the follicular phase of menstrual cycle. Sc bolus injection of saline or kisspeptin-54 (0·15, 0·30 or 0·60 nmol/kg) was administered 4 h after commencing the study. A previously described, blinded deconvolution method was used to detect LH pulses. Mean number of LH pulses was increased significantly following 0·30 and 0·60 nmol/kg kisspeptin-54 when compared with saline (mean increase in number of LH pulses per 4 h, following injection: -0·17 ± 0·54, saline; +2·33 ± 0·56, 0·30 nmol/kg kisspeptin-54, P 54, P 54, P = 0·10 vs saline). A single injection of kisspeptin-54 temporarily stimulates the number of LH pulses in healthy women. Further studies are required to investigate the therapeutic potential of kisspeptin-54 injection to restore LH pulsatility in patients with reproductive disorders caused by impaired GnRH secretion. © 2013 John Wiley & Sons Ltd.

  3. Melatonin Inhibits GnRH-1, GnRH-3 and GnRH Receptor Expression in the Brain of the European Sea Bass, Dicentrarchus labrax

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    José Antonio Muñoz-Cueto

    2013-04-01

    Full Text Available Several evidences supported the existence of melatonin effects on reproductive system in fish. In order to investigate whether melatonin is involved in the modulation of GnRH systems in the European sea bass, we have injected melatonin (0.5 µg/g body mass in male specimens. The brain mRNA transcript levels of the three GnRH forms and the five GnRH receptors present in this species were determined by real time quantitative PCR. Our findings revealed day–night variations in the brain expression of GnRH-1, GnRH-3 and several GnRH receptors (dlGnRHR-II-1c, -2a, which exhibited higher transcript levels at mid-light compared to mid-dark phase of the photocycle. Moreover, an inhibitory effect of melatonin on the nocturnal expression of GnRH-1, GnRH-3, and GnRH receptors subtypes 1c, 2a and 2b was also demonstrated. Interestingly, the inhibitory effect of melatonin affected the expression of hypophysiotrophic GnRH forms and GnRH receptors that exhibit day–night fluctuations, suggesting that exogenous melatonin reinforce physiological mechanisms already established. These interactions between melatoninergic and GnRH systems could be mediating photoperiod effects on reproductive and other rhythmic physiological events in the European sea bass.

  4. Gonadotropin-Releasing Hormone (GnRH) Receptor Structure and GnRH Binding.

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    Flanagan, Colleen A; Manilall, Ashmeetha

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) regulates reproduction. The human GnRH receptor lacks a cytoplasmic carboxy-terminal tail but has amino acid sequence motifs characteristic of rhodopsin-like, class A, G protein-coupled receptors (GPCRs). This review will consider how recent descriptions of X-ray crystallographic structures of GPCRs in inactive and active conformations may contribute to understanding GnRH receptor structure, mechanism of activation and ligand binding. The structures confirmed that ligands bind to variable extracellular surfaces, whereas the seven membrane-spanning α-helices convey the activation signal to the cytoplasmic receptor surface, which binds and activates heterotrimeric G proteins. Forty non-covalent interactions that bridge topologically equivalent residues in different transmembrane (TM) helices are conserved in class A GPCR structures, regardless of activation state. Conformation-independent interhelical contacts account for a conserved receptor protein structure and their importance in the GnRH receptor structure is supported by decreased expression of receptors with mutations of residues in the network. Many of the GnRH receptor mutations associated with congenital hypogonadotropic hypogonadism, including the Glu2.53(90) Lys mutation, involve amino acids that constitute the conserved network. Half of the ~250 intramolecular interactions in GPCRs differ between inactive and active structures. Conformation-specific interhelical contacts depend on amino acids changing partners during activation. Conserved inactive conformation-specific contacts prevent receptor activation by stabilizing proximity of TM helices 3 and 6 and a closed G protein-binding site. Mutations of GnRH receptor residues involved in these interactions, such as Arg3.50(139) of the DRY/S motif or Tyr7.53(323) of the N/DPxxY motif, increase or decrease receptor expression and efficiency of receptor coupling to G protein signaling, consistent with the native residues

  5. in seasonally anoestms GnRH-

    African Journals Online (AJOL)

    luteotrophic effect of progestogen priming followed by a multi- ple injection regime of GnRH. The life-span of corpora lutea induced by HCG was prolonged during postpartum anoestrus in cows pretreated with progesterone implants, but not in cows primed with oestradiol (pratt, Berardinelli, Stevens & Inskeep,. 1982).

  6. A Network Model of the Periodic Synchronization Process in the Dynamics of Calcium Concentration in GnRH Neurons

    Science.gov (United States)

    2013-01-01

    Mathematical neuroendocrinology is a branch of mathematical neurosciences that is specifically interested in endocrine neurons, which have the uncommon ability of secreting neurohormones into the blood. One of the most striking features of neuroendocrine networks is their ability to exhibit very slow rhythms of neurosecretion, on the order of one or several hours. A prototypical instance is that of the pulsatile secretion pattern of GnRH (gonadotropin releasing hormone), the master hormone controlling the reproductive function, whose origin remains a puzzle issue since its discovery in the seventies. In this paper, we investigate the question of GnRH neuron synchronization on a mesoscopic scale, and study how synchronized events in calcium dynamics can arise from the average electric activity of individual neurons. We use as reference seminal experiments performed on embryonic GnRH neurons from rhesus monkeys, where calcium imaging series were recorded simultaneously in tens of neurons, and which have clearly shown the occurrence of synchronized calcium peaks associated with GnRH pulses, superposed on asynchronous, yet oscillatory individual background dynamics. We design a network model by coupling 3D individual dynamics of FitzHugh–Nagumo type. Using phase-plane analysis, we constrain the model behavior so that it meets qualitative and quantitative specifications derived from the experiments, including the precise control of the frequency of the synchronization episodes. In particular, we show how the time scales of the model can be tuned to fit the individual and synchronized time scales of the experiments. Finally, we illustrate the ability of the model to reproduce additional experimental observations, such as partial recruitment of cells within the synchronization process or the occurrence of doublets of synchronization. PMID:23574739

  7. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow... device is placed in a cardiopulmonary bypass circuit downstream from the oxygenator. (b) Classification...

  8. Isosorbide dinitrate and pulsatile arterial haemodynamic variables in hypertension.

    Science.gov (United States)

    Levenson, J; Simon, A; Bouthier, J; Benetos, A; Safar, M E

    1986-10-01

    The effect of a sustained-release oral isosorbide dinitrate (ISDN) preparation on cerebral and forearm circulation was determined in 16 patients with mild to moderate essential hypertension. Measurements were made by pulsed Doppler velocimetry in the common carotid and the brachial arteries. Pulse wave velocity of the forearm was simultaneously recorded by means of strain gauge arterial mechanography allowing non-invasive evaluation of compliance and characteristic impedance of the brachial artery. Four hours after ISDN ingestion, the patients exhibited a significant decrease in blood pressure without a change in heart rate. An increase in carotid and brachial artery diameter was shown whereas blood flow increased only in the forearm. Resistance decreased significantly in both carotid and brachial vascular beds but only in the brachial vascular bed was the baseline resistance directly correlated with the change in brachial bed resistance. Concerning pulsatile large artery parameters, pulse wave velocity and characteristic impedance diminished, and brachial artery compliance increased significantly. The tangential tension of carotid and brachial arteries did not change. An increase in plasma renin activity was observed and related to the vasodilating effect on small arteries of the brachial vascular bed. This study showed that the antihypertensive effects of ISDN were accompanied by a strong vasodilatory action on small and large arteries and by an improvement in the pulsatile behaviour of large arteries.

  9. Pulsatile flow in model cerebral aneurysms

    NARCIS (Netherlands)

    Mikhal, Julia Olegivna; Geurts, Bernardus J.; Sato, Mitsuhisa; Matsuoka, Satoshi; Sloot, Peter M.; van Albada, G. Dick; Dongarra, Jack

    2011-01-01

    We present an immersed boundary method based on volume penalization, with which pulsatile flow in a model cerebral aneurysm is simulated. The model aneurysm consists of a curved vessel merged with a spherical cavity. The dominant vortical structures arising in the time-dependent flow are discussed

  10. Pulsatile Proptosis due to Intraorbital Meningocele.

    Science.gov (United States)

    van Rumund, Anouke; Verrips, Aad; Verhagen, Wim I M

    2017-01-01

    We present a case of a 79-year-old man with a non-symptomatic pulsatile proptosis of the left eye. Magnetic resonance imaging revealed a meningocele into the left orbit due to an osseous defect in the orbital roof.

  11. Pulsatile Proptosis due to Intraorbital Meningocele

    Directory of Open Access Journals (Sweden)

    Anouke van Rumund

    2017-06-01

    Full Text Available We present a case of a 79-year-old man with a non-symptomatic pulsatile proptosis of the left eye. Magnetic resonance imaging revealed a meningocele into the left orbit due to an osseous defect in the orbital roof.

  12. Pulsatile Proptosis due to Intraorbital Meningocele

    OpenAIRE

    Rumund, A. van; Verrips, A.; Verhagen, W.I.

    2017-01-01

    We present a case of a 79-year-old man with a non-symptomatic pulsatile proptosis of the left eye. Magnetic resonance imaging revealed a meningocele into the left orbit due to an osseous defect in the orbital roof.

  13. Optimisation of GnRH antagonist use in ART

    NARCIS (Netherlands)

    Hamdine, O.

    2014-01-01

    This thesis focuses on the optimisation of controlled ovarian stimulation for IVF using exogenous FSH and GnRH antagonist co-treatment, by studying the timing of the initiation of GnRH antagonist co-medication and the role of ovarian reserve markers in optimising ovarian response and reproductive

  14. GnRH injection before artificial insemination (AI) alters follicle ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... control group of Animals no injection of GnRH was performed. GnRH administered (Gonadorelin, 5 ml, intramuscular, made by. Aburaihan company, Tehran, Iran) on Day 6 of the estrous cycle. (estrus = Day 0). Ultrasonography examination. Ovarian follicular development was monitored daily by transrectal.

  15. GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET

    Directory of Open Access Journals (Sweden)

    Depalo Raffaella

    2012-04-01

    Full Text Available Abstract Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

  16. Chicken GnRH II occurs together with mammalian GnRH in a South American species of marsupial (Monodelphis domestica).

    Science.gov (United States)

    King, J A; Hinds, L A; Mehl, A E; Saunders, N R; Millar, R P

    1990-01-01

    Two molecular forms of gonadotropin-releasing hormone (GnRH) were demonstrated in hypothalamic extracts of M. domestica using high performance liquid chromatography and radioimmunoassay with specific GnRH antisera. One form eluted in the same position as synthetic mammalian GnRH and was quantified equally by two mammalian GnRH antisera, while the second form coeluted with synthetic chicken GnRH II and was quantified equally with two chicken GnRH II antisera. The finding of chicken GnRH II in a South American species of marsupial, which has previously been reported in some Australian species of marsupial and in species of Aves, Reptilia, Amphibia, Osteichthyes and Chondrichthyes, supports our hypothesis that this widespread structural variant may represent an early evolved and conserved form of GnRH.

  17. GnRH antagonist versus long agonist protocols in IVF

    DEFF Research Database (Denmark)

    Lambalk, C B; Banga, F R; Huirne, J A

    2017-01-01

    was not the only variable between the compared study arms. OBJECTIVE AND RATIONALE: The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. SEARCH...... METHODS: The Cochrane Menstrual Disorders and Subfertility Review Group specialized register of controlled trials and Pubmed and Embase databases were searched from inception until June 2016. Eligible trials were those that compared GnRH antagonist protocols and standard long GnRH agonist protocols...... the antagonist and agonist groups (RR 0.97, 95% CI 0.84-1.11 and RR 0.87, 95% CI 0.65-1.17, respectively). Subgroup analyses for various antagonist treatment schedules compared to the long protocol GnRH agonist showed a significantly lower ongoing pregnancy rate when the oral hormonal programming pill (OHP...

  18. GnRH tandem peptides for inducing an immunogenic response to GnRH-I without cross-reactivity to other GnRH isoforms

    NARCIS (Netherlands)

    Turkstra, J.A.; Schaaper, W.M.M.; Oonk, H.B.; Meloen, R.H.

    2005-01-01

    Gonadotropin releasing hormone (GnRH) occurs in various isoforms in mammals, i.e. GnRH-I (mammalian GnRH), GnRH-II (chicken GnRH-II), GnRH-III (salmon GnRH) and two forms of lamprey GnRH. The function of the latter four molecules have only been partially investigated. Also not much is known about

  19. Chromatographic and immunological evidence for mammalian GnRH and chicken GnRH II in eel (Anguilla anguilla) brain and pituitary.

    Science.gov (United States)

    King, J A; Dufour, S; Fontaine, Y A; Millar, R P

    1990-01-01

    Gonadotropin-releasing hormone (GnRH) peptides in the brain and pituitary of the European eel (Anguilla anguilla) were investigated by reverse phase high performance liquid chromatography (HPLC) and radioimmunoassay with region-specific antisera. Two GnRH molecular forms were demonstrated in brain and pituitary extracts. One form eluted in the same position as synthetic mammalian GnRH on HPLC and was recognized by antibodies directed against the NH2 and COOH termini of mammalian GnRH as well as by antibodies to the middle region. The second form eluted in the same position as synthetic chicken GnRH II and was recognized by specific antibodies to this molecule. Salmon GnRH and chicken GnRH I were not detected. The occurrence of mammalian GnRH in teleost fish suggests that this molecular form is more ancient than was previously suspected and arose earlier than in primitive tetrapods, or that it has arisen in the eel through random mutation of salmon GnRH. The lack of salmon GnRH in the eel brain indicates that this molecular form is not common to all teleost species. The finding in eel brain of chicken GnRH II, which has previously been described in species of Mammalia, Aves, Reptilia, Amphibia, Osteichthyes, and Chondrichthyes, supports our hypothesis that this widespread structural variant may represent an early evolved and conserved form of GnRH.

  20. A second form of gonadotropin-releasing hormone (GnRH), with chicken GnRH II-like properties, occurs together with mammalian GnRH in marsupial brains.

    Science.gov (United States)

    King, J A; Mehl, A E; Tyndale-Biscoe, C H; Hinds, L; Millar, R P

    1989-11-01

    GnRH peptides in the hypothalami of marsupials (tammar wallaby, short-nosed bandicoot, and eastern quoll) and a monotreme (echidna) were investigated by reverse phase HPLC and RIA with region-specific antisera. In the wallaby hypothalamic extract, a single form of GnRH was present, which eluted in the same position as synthetic mammalian GnRH on HPLC and was recognized by antibodies directed against the NH2- and COOH-termini of mammalian GnRH as well as by antibodies to the middle region. Two GnRH molecular forms were demonstrated in the bandicoot and quoll hypothalamic extracts. One form eluted in the same position as synthetic mammalian GnRH on HPLC and was quantified equally by two mammalian GnRH antisera. The second form eluted in the same position as synthetic chicken GnRH II and was recognized by specific antibodies to this molecule. Quantification of this immunoreactive peak with two chicken GnRH II antisera was not equal, suggesting that the peptide has similar properties to, but may not be identical to, chicken GnRH II. Immunoreactive GnRH was also detected in the echidna hypothalamic extract. These findings demonstrate that in some mammals more than one form of GnRH is present in the brain of a single species, as has previously been found in species from all nonmammalian vertebrate classes. The finding in marsupial brain of a peptide with properties of chicken GnRH II, which has previously been reported in species of Aves, Reptilia, Amphibia, Osteichthyes, and Chondrichthyes, supports our hypothesis that this widespread structural variant may represent an early early evolved and conserved form of GnRH.

  1. Positron emission particle tracking in pulsatile flow

    Science.gov (United States)

    Patel, Nitant; Wiggins, Cody; Ruggles, Arthur

    2017-05-01

    Positron emission particle tracking (PEPT) is increasingly used to understand the flow characteristics in complex systems. This research utilizes PEPT to measure pulsatile flow of frequency 2.1 Hz in an elastic Masterkleer PVC tube of 19 mm inner diameter and 3.2 mm wall thickness. Anion exchange resin beads are labeled with 18F and delivered to a pump driven flow loop with motorized ball valve used to develop the pulsatile flow. Data are collected in the tube with circular cross section, and measurements are also collected with a section of the tube pinched. Nominal flow velocities are near 1 m/s and Reynolds numbers near 20,000. Many thousand PEPT particle traces are collected and synchronized with the flow pulsation. These Lagrangian data are presented as a series of 20 still frames depicting the 3-D velocity field present during each phase of the flow pulsation. Pressure data are also collected to resolve the pressure wave front moving through the open elastic tube at velocity 15.2 m/s.

  2. Positron emission particle tracking in pulsatile flow

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Nitant; Ruggles, Arthur [University of Tennessee-Knoxville, Department of Nuclear Engineering, Knoxville, TN (United States); Wiggins, Cody [University of Tennessee-Knoxville, Department of Physics and Astronomy, Knoxville, TN (United States)

    2017-05-15

    Positron emission particle tracking (PEPT) is increasingly used to understand the flow characteristics in complex systems. This research utilizes PEPT to measure pulsatile flow of frequency 2.1 Hz in an elastic Masterkleer PVC tube of 19 mm inner diameter and 3.2 mm wall thickness. Anion exchange resin beads are labeled with {sup 18}F and delivered to a pump driven flow loop with motorized ball valve used to develop the pulsatile flow. Data are collected in the tube with circular cross section, and measurements are also collected with a section of the tube pinched. Nominal flow velocities are near 1 m/s and Reynolds numbers near 20,000. Many thousand PEPT particle traces are collected and synchronized with the flow pulsation. These Lagrangian data are presented as a series of 20 still frames depicting the 3-D velocity field present during each phase of the flow pulsation. Pressure data are also collected to resolve the pressure wave front moving through the open elastic tube at velocity 15.2 m/s. (orig.)

  3. Pulsatile flow in ventricular catheters for hydrocephalus

    Science.gov (United States)

    Giménez, Á.; Galarza, M.; Thomale, U.; Schuhmann, M. U.; Valero, J.; Amigó, J. M.

    2017-05-01

    The obstruction of ventricular catheters (VCs) is a major problem in the standard treatment of hydrocephalus, the flow pattern of the cerebrospinal fluid (CSF) being one important factor thereof. As a first approach to this problem, some of the authors studied previously the CSF flow through VCs under time-independent boundary conditions by means of computational fluid dynamics in three-dimensional models. This allowed us to derive a few basic principles which led to designs with improved flow patterns regarding the obstruction problem. However, the flow of the CSF has actually a pulsatile nature because of the heart beating and blood flow. To address this fact, here we extend our previous computational study to models with oscillatory boundary conditions. The new results will be compared with the results for constant flows and discussed. It turns out that the corrections due to the pulsatility of the CSF are quantitatively small, which reinforces our previous findings and conclusions. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

  4. Effect of a single injection of gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) on testicular blood flow measured by color doppler ultrasonography in male Shiba goats.

    Science.gov (United States)

    Samir, Haney; Sasaki, Kazuaki; Ahmed, Eman; Karen, Aly; Nagaoka, Kentaro; El Sayed, Mohamed; Taya, Kazuyoshi; Watanabe, Gen

    2015-05-01

    Although color Doppler ultrasonography has been used to evaluate testicular blood flow in many species, very little has been done in goat. Eight male Shiba goats were exposed to a single intramuscular injection of either gonadotropin-releasing hormone (GnRH group; 1 µg/kg BW) or human chorionic gonadotropin (hCG group; 25 IU/kg BW). Plasma testosterone (T), estradiol (E2) and inhibin (INH) were measured just before (0 hr) and at different intervals post injection by radioimmunoassay. Testis volume (TV) and Doppler indices, such as resistive index (RI) and pulsatility index (PI) of the supratesticular artery, were measured by B-mode and color Doppler ultrasonography, respectively. The results indicated an increase in testicular blood flow in both groups, as RI and PI decreased significantly (P<0.05), but this increase was significant higher and earlier in hCG group (1 hr) than in the GnRH group (2 hr). A high correlation was found for RI and PI with both T (RI, r= -0.862; PI, r= -0.707) and INH in the GnRH group (RI, r=0.661; PI, r=0.701). However, a significant (P<0.05) correlation was found between E2 and both RI (r= -0.610) and PI (r= -0.763) in hCG group. In addition, TV significantly increased and was highly correlated with RI in both groups (GnRH, r= -0.718; hCG, r= -0.779). In conclusion, hCG and GnRH may improve testicular blood flow and TV in Shiba goats.

  5. A novel rotary pulsatile flow pump for cardiopulmonary bypass.

    Science.gov (United States)

    Teman, Nicholas R; Mazur, Daniel E; Toomasian, John; Jahangir, Emilia; Alghanem, Fares; Goudie, Marcus; Rojas-Peña, Alvaro; Haft, Jonathan W

    2014-01-01

    It has been suggested that pulsatile blood flow is superior to continuous flow (CF) in cardiopulmonary bypass (CPB). However, adoption of pulsatile flow (PF) technology has been limited because of practicality and complexity of creating a consistent physiologic pulse. A pediatric pulsatile rotary ventricular pump (PRVP) was designed to address this problem. We evaluated the PRVP in an animal model and determined its ability to generate PF during CPB. The PRVP (modified peristaltic pump, with tapering of the outlet of the pump chamber) was tested in four piglets (10-12 kg). Cannulation was performed with right atrial and aortic cannulae, and pressure sensors were inserted into the femoral arteries. Pressure curves were obtained at different levels of flow and compared with both the animal's baseline physiologic function and a CF roller pump. Pressure and flow waveforms demonstrated significant pulsatility in the PRVP setup compared with CF at all tested conditions. Measurement of hemodynamic energy data, including the percentage pulsatile energy and the surplus hydraulic energy, also revealed a significant increase in pulsatility with the PRVP (p < 0.001). The PRVP creates physiologically significant PF, similar to the pulsatility of a native heart, and has the potential to be easily implemented in pediatric CPB.

  6. Recent Development of Non-Peptide GnRH Antagonists

    Directory of Open Access Journals (Sweden)

    Feng-Ling Tukun

    2017-12-01

    Full Text Available The decapeptide gonadotropin-releasing hormone, also referred to as luteinizing hormone-releasing hormone with the sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 plays an important role in regulating the reproductive system. It stimulates differential release of the gonadotropins FSH and LH from pituitary tissue. To date, treatment of hormone-dependent diseases targeting the GnRH receptor, including peptide GnRH agonist and antagonists are now available on the market. The inherited issues associate with peptide agonists and antagonists have however, led to significant interest in developing orally active, small molecule, non-peptide antagonists. In this review, we will summarize all developed small molecule GnRH antagonists along with the most recent clinical data and therapeutic applications.

  7. Pituitary sensitizing effect of GnRH antagonists: a mechanism explaining LH escape during IVF?

    NARCIS (Netherlands)

    Banga, F.R.; Huirne, J.A.F.; Korsen, T.; Homburg, R.R.; Hompes, P.G.A.; Lambalk, C.B.

    2010-01-01

    Background GnRH antagonists have been introduced to induce persistent LH suppression. Many studies show a gradual increase of LH levels after several days of GnRH antagonist administration, the so-called escape or rebound effect. We hypothesize that, under chronic GnRH antagonist administration, a

  8. Effects of GnRH immunization in sexually mature pony stallions

    NARCIS (Netherlands)

    Turkstra, J.A.; Meer, F.J.U.M.; Knaap, J.; Rottier, P.J.M.; Teerds, K.J.; Colenbrander, B.; Meloen, R.H.

    2005-01-01

    Immunization against gonadotrophin releasing hormone (GnRH) was studied as an alternative for the commonly used surgical castration in stallions. Two GnRH vaccines comprising non-mineral oil adjuvants were evaluated for their potential to induce high antibody titers directed against GnRH and

  9. [Preparation of Shuxiong pulsatile controlled-release dropping pill].

    Science.gov (United States)

    Chen, Hui; Chen, Yan-Zhong; Xie, Qing-Chun; Lin, Shi-Yuan; Lin, Jia-Cheng; Jianc, Wei-Ning

    2013-07-01

    To prepare Shuxiong pulsatile controlled-release dropping pill and study the influencing factors in vitro. Dropping pills with suitable size (10 - 15 mg) were coated with swelling layer containing croscarmellose sodium and controlled-release layer containing ethylcellulos aqueous dispersion respectively to prepare Shuxiong pulsatile controlled-release dropping pill. The effects of the materials of swelling layer, the weight of swelling layer and controlled-release layer on the release of drugs were investigated to optimize the process technology and validate formula. The release behavior was influenced strikingly by the types and weight of coating layer. The optimal formula was as follows: Shuxiong pulsatile controlled-release dropping pills were prepared using croscarmellose sodium as inner layer with 15% (weight) coating level and ethylcellulose aqueous dispersion (Surelease) as outer controlled-release layer with 7% (weight) coating level. The lag time of prepared pulsatile controlled-release dropping pills was about 4 h and accumulative release rate reached 80% within 4 h. The drug release of Shuxiong pulsatile controlled-release dropping pill is shown in pulsatile way in vitro.

  10. Optimum Heart Rate to Minimize Pulsatile External Cardiac Power

    Science.gov (United States)

    Pahlevan, Niema; Gharib, Morteza

    2011-11-01

    The workload on the left ventricle is composed of steady and pulsatile components. Clinical investigations have confirmed that an abnormal pulsatile load plays an important role in the pathogenesis of left ventricular hypertrophy (LVH) and progression of LVH to congestive heart failure (CHF). The pulsatile load is the result of the complex dynamics of wave propagation and reflection in the compliant arterial vasculature. We hypothesize that aortic waves can be optimized to reduce the left ventricular (LV) pulsatile load. We used an in-vitro experimental approach to investigate our hypothesis. A unique hydraulic model was used for in-vitro experiments. This model has physical and dynamical properties similar to the heart-aorta system. Different compliant models of the artificial aorta were used to test the hypothesis under various aortic rigidities. Our results indicate that: i) there is an optimum heart rate that minimizes LV pulsatile power (this is in agreement with our previous computational study); ii) introducing an extra reflection site at the specific location along the aorta creates constructive wave conditions that reduce the LV pulsatile power.

  11. Dynamic GnRH- and hCG-testing

    DEFF Research Database (Denmark)

    Bang, A Kirstine; Nordkap, Loa; Almstrup, Kristian

    2017-01-01

    1. OBJECTIVE: Gonadotropin-releasing hormone (GnRH) and Human Chorionic Gonadotropin (hCG) stimulation-tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and Testosterone after GnRH...... and hCG stimulation in healthy men, and assess the impact of six single nucleotide polymorphisms on the responses. 2. DESIGN: GnRH- and hCG-stimulation tests were performed on 77 healthy men, 18-40 years (reference group) at a specialized andrology referral center. The potential use of the tests...... and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4-58.8 U/L and 0.2-11.8 U/L, FSH decreased in nine men. Testosterone increased approximately 110% (range 18.7-67.6 nmol/l) during hCG-testing. None of the polymorphisms had any major impact on the test results...

  12. Pharmacological and toxicological assessment of a potential GnRH vaccine in young-adult male pigs

    NARCIS (Netherlands)

    Turkstra, J.A.; Staay, van der F.J.; Stockhofe-Zurwieden, N.; Woelders, H.; Meloen, R.H.; Schuurman, T.

    2011-01-01

    Active immunization against gonadotrophin-releasing hormone (GnRH) is successfully applied to prevent boar taint in pork. In men, GnRH immunization could be an alternative to hormone therapy in patients with prostate cancer. In this study, a new GnRH vaccine formulation (a modified GnRH peptide

  13. LH-independent testosterone secretion is mediated by the interaction between GNRH2 and its receptor within porcine testes

    Science.gov (United States)

    Unlike the classical gonadotropin-releasing hormone (GNRH1), the second mammalian isoform (GNRH2) is an ineffective stimulant of gonadotropin release. Species that produce GNRH2 may not maintain a functional GNRH2 receptor (GNRHR2) due to coding errors. A full length GNRHR2 gene has been identified ...

  14. The role of GABA in the regulation of GnRH neurons

    Directory of Open Access Journals (Sweden)

    Miho eWatanabe

    2014-11-01

    Full Text Available Gonadotropin-releasing hormone (GnRH neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA. While many reports have provided much insight into the contribution of GABA to the activity of GnRH neurons, the precise physiological role of the excitatory action of GABA on GnRH neurons remains elusive. This brief review presents the current knowledge of the role of GABA signaling in GnRH neuronal activity. We also discuss the modulation of GABA signaling by neurotransmitters and neuromodulators and the functional consequence of GABAergic inputs to GnRH neurons in both the physiology and pathology of reproduction.

  15. Regulation versus modulation in GnRH receptor function

    Energy Technology Data Exchange (ETDEWEB)

    Zolman, J.C.; Theodoropoulos, T.J.

    1985-03-01

    Serum luteinizing hormone (LH) concentration after exposure to gonadotropin-releasing hormone (GnRH) indicates that an instantaneous increase occurs in the rate of release of LH directly from the anterior pituitary, as measured dynamically during superfusion in vitro. On the other hand, estradiol-17 beta (E2) alone shows no such instantaneous effect on LH release rate (at least for the first four hours), in either physiologic or pharmacologic concentrations. At the same time, brief (ten to 30 minute) exposure of isolated anterior pituitary plasma membranes to physiologic concentrations of E2 significantly alters the binding of a fully biologically active /sup 125/I-GnRH to its plasma membrane receptor protein. In order to characterize the effect of E2 on GnRH binding further, dispersed bovine anterior pituitary cells were preincubated for six hours in the presence or absence of physiologic concentrations of E2 (10(-10)M). Following preincubation in the presence of E2, the cell suspension was incubated for 30 minutes with physiologic concentrations (5 x 10(-11) - 5 x 10(-10)M) of a fully biologically active /sup 125/I-GnRH. The treatment, at least, doubled the number of biologically important high affinity GnRH binding sites (Kd's . 7.5 x -10(-11) - 4.5 x 10(-10)M), and changed the binding capacity of some of the binding sites up to three fold, which altered the cooperativity of GnRH-receptor interaction. Thus, the interaction of E2 with GnRH at the level of GnRH receptor is mandatory for the short-term pituitary effect of E2 on LH release in vitro and in vivo.

  16. Estrogenic Regulation of the GnRH Neuron

    Directory of Open Access Journals (Sweden)

    Sally eRadovick

    2012-04-01

    Full Text Available Reproductive function is regulated by the secretion of luteinizing hormone (LH and follicle-stimulating hormone (FSH from the pituitary and the steroid hormones from the gonads. The dynamic changes in the levels of the reproductive hormones regulate secondary sex characteristics, gametogenesis, cellular function and behavior. Hypothalamic GnRH neurons, with cell bodies located in the basal hypothalamus, represent the final common pathway for neuronally derived signals to the pituitary. As such, they serve as integrators of a dizzying array of signals including sensory inputs mediating information about circadian, seasonal, behavioral, pheromonal and emotional cues. Additionally, information about peripheral physiological function may also be included in the integrative signal to the GnRH neuron. These signals may communicate information about metabolic status, disease or infection. Gonadal steroid hormones arguably exert the most important effects on GnRH neuronal function. In both males and females, the gonadal steroid hormones exert negative feedback regulation on axis activity at both the level of the pituitary and the hypothalamus. These negative feedback loops regulate homeostasis of steroid hormone levels. In females, a cyclic reversal of estrogen feedback produces a positive feedback loop at both the hypothalamic and pituitary levels. Central positive feedback results in a dramatic increase in GnRH secretion (Sisk and others 2001; Clarke 1993; Moenter, Brand and Karsch 1992; Xia and others 1992. This is coupled with an increase in pituitary sensitivity to GnRH (Turzillo, DiGregorio and Nett 1995; Savoy-Moore and others 1980, which produces the massive surge in secretion of LH that triggers ovulation.

  17. Insulin pulsatility after the intravenous glucose bolus

    Directory of Open Access Journals (Sweden)

    Nedeljković-Beleslin Biljana

    2016-01-01

    Full Text Available OBJECTIVE: The aim of the study was to assess whether sudden change in blood glucose concentration in healthy subject would produce insulin secretory pattern similar to one in type 2 diabetic subjects (T2D. DESIGN: The concept of the study was to 'reset' the pancreas and empty the stored insulin pool, so that subtle derangements of the pulsatile insulin secretion could be studied. METHODS: The study group included 6 control and 7 T2D subjects. For insulin and glucose determination, blood was sampled for 60 minutes with 2 minutes inter-sample interval. To increase blood glucose an intravenous glucose bolus was given (0.3 g/kg body weight. RESULTS: The average glucose level in the T2D group was significantly higher, but the average insulin concentration was not different between the groups. Insulin half-life, pulse amplitude, number of pulses and interpulse interval did not differ between the groups. CONCLUSIONS: Therefore, the sudden increase in blood glucose causes insulin secretory pattern to become similar in the healthy and in the T2D subjects. However, the defect in the insulin secretion or glucose sensing inherent to β-cell exists, as the insufficient quantity of insulin is secreted in response to the increased glucose level.

  18. Arduino control of a pulsatile flow rig.

    Science.gov (United States)

    Drost, S; de Kruif, B J; Newport, D

    2018-01-01

    This note describes the design and testing of a programmable pulsatile flow pump using an Arduino micro-controller. The goal of this work is to build a compact and affordable system that can relatively easily be programmed to generate physiological waveforms. The system described here was designed to be used in an in-vitro set-up for vascular access hemodynamics research, and hence incorporates a gear pump that delivers a mean flow of 900 ml/min in a test flow loop, and a peak flow of 1106 ml/min. After a number of simple identification experiments to assess the dynamic behaviour of the system, a feed-forward control routine was implemented. The resulting system was shown to be able to produce the targeted representative waveform with less than 3.6% error. Finally, we outline how to further increase the accuracy of the system, and how to adapt it to specific user needs. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  19. Effects of Pulsatile Blood Flow on Oxygenator Performance.

    Science.gov (United States)

    Schraven, Lotte; Kaesler, Andreas; Flege, Christian; Kopp, Rüdger; Schmitz-Rode, Thomas; Steinseifer, Ulrich; Arens, Jutta

    2018-02-13

    Extracorporeal membrane oxygenation (ECMO) is mainly used for the therapy of acute respiratory distress syndrome and chronic obstructive lung disease. In the last years, the development of these systems underwent huge steps in optimization, but there are still problems with thrombus formation, clogging, and thus insufficient gas exchange. One idea of ECMO optimization is a pulsatile blood flow through the oxygenator, but this is still a controversy discussion. Analyzing available publications, it was not possible to identify a general statement about the effect of pulsatile blood flow on the gas exchange performance. The variety of parameters and circuit components have such a high influence on the outcome that a direct comparison of the studies is difficult. For this reason, we performed a structured study to evaluate the effects of pulsatile blood flow on the gas exchange performance of oxygenator. In in vitro tests according to DIN EN ISO 7199, we tested a small oxygenator (0.25 m 2 exchange surface, polymethylpentene fibers, 33 mL priming volume) with constant and pulsatile blood flow in comparison. Therefore, we varied the mean blood flow from 250 to 1200 mL/min, the amplitude of 0, 20, and 50%, and the frequency of 30, 60, and 90 bpm. The results demonstrate that the gas transfer for pulsatile and constant blood flow was similar (oxygen: 36-64 mL O2 /L Blood ; carbon dioxide 35-80 mL CO2 /L Blood ) for the same mean blood flow ranges. Over all, the results and analyses showed a statistically nonsignificant difference between pulsatile and nonpulsatile flow. Consequently, we conclude that the implementation of pulsatile blood flow has only a small to no effect on the gas exchange performance in an oxygenator. As the results were obtained using an oxygenator with a coiled fiber bundle, the test must be verified for a stacked fiber oxygenator. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  20. Encoding and decoding mechanisms of pulsatile hormone secretion.

    Science.gov (United States)

    Walker, J J; Terry, J R; Tsaneva-Atanasova, K; Armstrong, S P; McArdle, C A; Lightman, S L

    2010-12-01

    Ultradian pulsatile hormone secretion underlies the activity of most neuroendocrine systems, including the hypothalamic-pituitary adrenal (HPA) and gonadal (HPG) axes, and this pulsatile mode of signalling permits the encoding of information through both amplitude and frequency modulation. In the HPA axis, glucocorticoid pulse amplitude increases in anticipation of waking, and, in the HPG axis, changing gonadotrophin-releasing hormone pulse frequency is the primary means by which the body alters its reproductive status during development (i.e. puberty). The prevalence of hormone pulsatility raises two crucial questions: how are ultradian pulses encoded (or generated) by these systems, and how are these pulses decoded (or interpreted) at their target sites? We have looked at mechanisms within the HPA axis responsible for encoding the pulsatile mode of glucocorticoid signalling that we observe in vivo. We review evidence regarding the 'hypothalamic pulse generator' hypothesis, and describe an alternative model for pulse generation, which involves steroid feedback-dependent endogenous rhythmic activity throughout the HPA axis. We consider the decoding of hormone pulsatility by taking the HPG axis as a model system and focussing on molecular mechanisms of frequency decoding by pituitary gonadotrophs. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.

  1. GnRH agonist for triggering of final oocyte maturation

    DEFF Research Database (Denmark)

    Al Humaidan, Peter Samir Heskjær; Kol, S; Papanikolaou, E G

    2011-01-01

    GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase...... deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering....

  2. Using GnRH to Improve Cow Fecundity after Calving

    Directory of Open Access Journals (Sweden)

    Nicolae Păcală

    2012-05-01

    Full Text Available At dairy cows, the increase in milk production is associated with the decrease of heat manifestation and conception rates. GnRH is mostly used for treatment of different problems of the reproductive function and for improving the pregnancy rates in cows. The aim of our paper was to contribute to increase of conception rates, at cows with ovarian activity, at first AI after calving. The experiments were conducted on 58 cows, from Romanian Black Spotted breed (Frezian and 53 cows from Romanian Spotted breed (Simmental. The animals were divided into lots as follows: for Romanian Black Spotted breed 33 of the cows in were in experimental lot and 25 were in control lot, for Romanian Spotted breed 29 ere in experimental lot and 24 were in control lot. The females form experimental lots were treated with 100 mcg (2ml Ovarelin (GnRH, at the first AI, after VWP. At the cows form Romanian Black Spotted, from the 33 females in experimental lot, 12 did not return into heat after insemination, which represents a conception rate of 36.4%. At the cows form Romanian Spotted, form the 29 cows in experimental lot 8 did not return into heat after insemination, representing a conception rate of 44.8%. Administration of 100 mcg GnRH (2 ml Ovarelin at the time of AI determines a significant increase of the conception rate with 8.4-11.5%, compared with control lot. It appears that the cows from Romanian Spotted reacts better at GnRH treatment (44.8% conception rate, compared with Romanian Black Spotted (36.4 % conception rate.

  3. The influence of 17beta-oestradiol on corticotrophin-releasing hormone induced suppression of luteinising hormone pulses and the role of CRH in hypoglycaemic stress-induced suppression of pulsatile LH secretion in the female rat.

    Science.gov (United States)

    Cates, P S; Li, X F; O'Byrne, K T

    2004-06-01

    Corticotrophin-releasing hormone (CRH) released during stress has been implicated in the disruption of the reproductive neuroendocrine axis, and 17beta-oestradiol (E2) has been shown to enhance stress-induced suppression of pulsatile gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) release. The aims of the present study were to examine the role of CRH in hypoglycaemic stress-induced suppression of LH pulses, and to investigate the influence of E2 on the inhibitory effect of CRH on pulsatile LH secretion in the female rat. Suppression of LH pulses by insulin-induced hypoglycaemic (IIH) stress was completely prevented by intracerebroventricular (icv) administration of a CRH antagonist. Central administration of CRH (5 microg) resulted in an interruption of LH pulses in E2 treated animals, but had little or no effect in the absence of this gonadal steroid. These results provide evidence of a pivotal role for CRH in mediating the suppressive effect of IIH stress on pulsatile LH secretion in the female rat, and highlight a sensitising role for E2 in CRH-induced suppression of LH pulses.

  4. Differential effects of continuous exposure to the investigational metastin/kisspeptin analog TAK-683 on pulsatile and surge mode secretion of luteinizing hormone in ovariectomized goats.

    Science.gov (United States)

    Tanaka, Tomomi; Ohkura, Satoshi; Wakabayashi, Yoshihiro; Kuroiwa, Takenobu; Nagai, Kiyosuke; Endo, Natsumi; Tanaka, Akira; Matsui, Hisanori; Kusaka, Masami; Okamura, Hiroaki

    2013-12-17

    The aim of the present study was to determine if the estradiol-induced luteinizing hormone (LH) surge is influenced by the constant exposure to TAK-683, an investigational metastin/kisspeptin analog, that had been established to depress the pulsatile gonadotropin-releasing hormone (GnRH) and LH secretion in goats. Ovariectomized goats subcutaneously received TAK-683 (TAK-683 group, n=6) or vehicle (control group, n=6) constantly via subcutaneous implantation of an osmotic pump. Five days after the start of the treatment, estradiol was infused intravenously in both groups to evaluate the effects on the LH surge. Blood samples were collected at 6-min intervals for 4 h prior to the initiation of either the TAK-683 treatment or the estradiol infusion, to determine the profiles of pulsatile LH secretion. They were also collected at 2-h intervals from -4 h to 32 h after the start of estradiol infusion for analysis of LH surges. The frequency and mean concentrations of LH pulses in the TAK-683 group were remarkably suppressed 5 days after the start of TAK-683 treatment compared with those of the control group (Psurge was observed in all animals of both groups. There were no significant differences in the LH concentrations for surge peak and the peak time of the LH surge between the TAK-683 and control groups. These findings suggest that the effects of continuous exposure to kisspeptin or its analog on the mechanism(s) that regulates the pulsatile and surge mode secretion of GnRH/LH are different in goats.

  5. Impaired crosstalk between pulsatile insulin and glucagon secretion in prediabetic individuals

    DEFF Research Database (Denmark)

    Rohrer, Stefan; Menge, Björn A; Grüber, Lena

    2012-01-01

    Postprandial hyperglucagonemia is frequently found in patients with diabetes. Recently, a loss of the inverse relationship between pulsatile insulin and glucagon secretion has been reported in patients with type 2 diabetes. The crosstalk between pulsatile islet hormone secretion in prediabetic...

  6. Generation of tunable and pulsatile concentration gradients via microfluidic network

    KAUST Repository

    Zhou, Bingpu

    2014-06-04

    We demonstrate a compact Polydimethylsiloxane microfluidic chip which can quickly generate ten different chemical concentrations simultaneously. The concentration magnitude of each branch can be flexibly regulated based on the flow rate ratios of the two injecting streams. The temporal/pulsatile concentration gradients are achieved by integrating on-chip pneumatic actuated valves controlled by the external signals. The temporal concentration gradients can also be tuned precisely by varying applied frequency and duty cycle of the trigger signal. It is believed that such microdevice will be potentially used for some application areas of producing stable chemical gradients as well as allowing fast, pulsatile gradient transformation in seconds.

  7. Loss of inverse relationship between pulsatile insulin and glucagon secretion in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Menge, Björn A; Grüber, Lena; Jørgensen, Signe M

    2011-01-01

    In patients with type 2 diabetes, glucagon levels are often increased. Furthermore, pulsatile secretion of insulin is disturbed in such patients. Whether pulsatile glucagon secretion is altered in type 2 diabetes is not known.......In patients with type 2 diabetes, glucagon levels are often increased. Furthermore, pulsatile secretion of insulin is disturbed in such patients. Whether pulsatile glucagon secretion is altered in type 2 diabetes is not known....

  8. Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH neurons

    Directory of Open Access Journals (Sweden)

    Christian Cortés-Campos

    2015-09-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.

  9. Does the location of a vascular loop in the cerebellopontine angle explain pulsatile and non-pulsatile tinnitus?

    Energy Technology Data Exchange (ETDEWEB)

    Nowe, V.; Wang, X.L.; Gielen, J.; Goethem, J.Van; Oezsarlak, Oe.; De Schepper, A.M.; Parizel, P.M. [University of Antwerp, Department of Radiology, Edegem (Belgium); Ridder, D. De [University of Antwerp, Department of Neurosurgery, Edegem (Belgium); Heyning, P.H.Van de [University of Antwerp, Department of Otorhinolaryngology, Edegem (Belgium)

    2004-12-01

    The purpose was to investigate patients with unexplained pulsatile and non-pulsatile tinnitus by means of MR imaging of the cerebellopontine angle (CPA) and to correlate the clinical subtype of tinnitus with the location of a blood vessel (in the internal auditory canal or at the cisternal part of the VIIIth cranial nerve). Clinical presentation of tinnitus and perceptive hearing loss were correlated. In 47 patients with unexplained tinnitus, an MR examination of the CPA was performed. Virtual endoscopy reconstructions were obtained using a 3D axial thin-section high-resolution heavily T2-weighted gradient echo constructive interference in steady state (CISS) data-set. High-resolution T2-weighted CISS images showed a significantly higher number of vascular loops in the internal auditory canal in patients with arterial pulsatile tinnitus compared to patients with non-pulsatile tinnitus (P<0.00001). Virtual endoscopy images were used to investigate vascular contacts at the cisternal part of the VIIIth cranial nerve in patients with low pitch and high pitch non-pulsatile tinnitus. A significantly different distribution of the vascular contacts (P=0.0320) was found. Furthermore, a correlation between the clinical presentation of non-pulsatile tinnitus (high pitch and low pitch) and the perceptive hearing loss was found (P=0.0235). High-resolution heavily T2-weighted CISS images and virtual endoscopy of the CPA can be used to evaluate whether a vascular contact is present in the internal auditory canal or at the cisternal part of the VIIIth cranial nerve and whether the location of the vascular contact correlates with the clinical subtype of tinnitus. Our findings suggest that there is a tonotopical structure of the cisternal part of the VIIIth cranial nerve. A correlation between the clinical presentation of tinnitus and hearing loss was found. (orig.)

  10. Targeted Mutagenesis of the Hypophysiotropic Gnrh3 in Zebrafish (Danio rerio Reveals No Effects on Reproductive Performance.

    Directory of Open Access Journals (Sweden)

    Olivia Smith Spicer

    Full Text Available Gnrh is the major neuropeptide regulator of vertebrate reproduction, triggering a cascade of events in the pituitary-gonadal axis that result in reproductive competence. Previous research in mice and humans has demonstrated that Gnrh/GNRH null mutations result in hypogonadotropic hypogonadism and infertility. The goal of this study was to eliminate gnrh3 (the hypophysiotropic Gnrh form function in zebrafish (Danio rerio to determine how ontogeny and reproductive performance are affected, as well as factors downstream of Gnrh3 along the reproductive axis. Using the TALEN technology, we developed a gnrh3-/- zebrafish line that harbors a 62 bp deletion in the gnrh3 gene. Our gnrh3-/- zebrafish line represents the first targeted and heritable mutation of a Gnrh isoform in any organism. Using immunohistochemistry, we verified that gnrh3-/- fish do not possess Gnrh3 peptide in any regions of the brain. However, other than changes in mRNA levels of pituitary gonadotropin genes (fshb, lhb, and cga during early development, which are corrected by adulthood, there were no changes in ontogeny and reproduction in gnrh3-/- fish. The gnrh3-/- zebrafish are fertile, displaying normal gametogenesis and reproductive performance in males and females. Together with our previous results that Gnrh3 cell ablation causes infertility, these results indicate that a compensatory mechanism is being activated, which is probably primed early on upon Gnrh3 neuron differentiation and possibly confined to Gnrh3 neurons. Potential compensation factors and sensitive windows of time for compensation during development and puberty should be explored.

  11. A pulsatile developing flow in a bend

    Science.gov (United States)

    Thiriet, M.; Graham, J. M. R.; Issa, R. I.

    1992-06-01

    Low frequency pulsatile flow of an incompressible viscous fluid has been numerically investigated in a rigid 90° bend of circular cross-section, using the finite-volume method. The governing parameters are as follows : amplitude ratio of 1.25, Womersley parameter of 4, peak Reynolds number of 358, peak Dean number of 113, Strouhal number ranging from 0.05 to 0.45. With this set of input data, no flow reversal is observed and a single axial vortex occurs in the half cross-section. Upstream and downstream effects of the bend are mainly characterized by an inward shift of the peak axial velocity in the upstream straight tube and the persistency of the secondary motions several diameters down the exit straight pipe. Secondary motions, present in steady flow, weaken greatly when the unsteady axial component of the flow (W) is lower than the mean flow bar{W}. The axial shear stress tau_a, whose maximum is more often located at the outer part of the bend, increases and remains nearly constant about 8 diameters downstream from the bend inlet. The circumferential shear stress tau_c maximum, located slightly towards the outer bend, is 28% of tau_a maximum, and 20% when W W, and locally at the inner edge. Un écoulement pulsé à basse fréquence d'un fluide incompressible visqueux a été étudié numériquement dans un coude, à 90°, de parois rigides et de section droite circulaire et constante, par la méthode des volumes finis. Les valeurs des paramètres adimensionnels gouvernant l'écoulement sont: un rapport d'amplitude de 1,25, un paramètre de Womersley de 4, un nombre de Reynolds crête de 358, un nombre de Dean crête de 113; le nombre de Strouhal varie entre 0,05 et 0,45. Aucune inversion du courant principal n'est observé et un unique vortex dans chaque demi-section droite apparaît. Les effets sur les tubes droits, l'un précèdant et l'autre suivant le coude sont caractérisés par un décalage du pic de vitesse axiale vers le bord interne du tube en amont

  12. Leaback of Pulsatile Flow of Particle Fluid Suspension Model of ...

    African Journals Online (AJOL)

    The variation in body acceleration amplitude though affects the velocity profile in the capillary tubes, it has no effect on the leakback in the tubes. Leakback is mainly determined by the balance of the viscous drag and the driving force of the applied pressure gradient. Key words: Leakback, Pulsatile Flow, Fluid Suspension, ...

  13. Circadian changes in pulsatile TSH release in primary hypothyroidism

    NARCIS (Netherlands)

    Adriaanse, R.; Brabant, G.; Prank, K.; Endert, E.; Wiersinga, W. M.

    1992-01-01

    We evaluated pulsatile and circadian TSH secretion in primary hypothyroidism. In a prospective study, blood was sampled every 10 minutes during 24 hours for assay of TSH (IRMA). Thyroid hormones and TSH responsiveness to TRH were then measured. Nine patients with overt primary hypothyroidism, seven

  14. Nonlinear analysis and prediction of pulsatile hormone secretion

    Energy Technology Data Exchange (ETDEWEB)

    Prank, K. [Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, D-30623 Hannover (Germany)]|[Howard Hughes Medical Institute and Computational Neurobiology Laboratory, The Salk Institute, San Diego, California 92186-5800 (United States); Kloppstech, M. [Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, D-30623 Hannover (Germany); Nowlan, S.J. [Howard Hughes Medical Institute and Computational Neurobiology Laboratory, The Salk Institute, San Diego, California 92186-5800 (United States); Harms, H.M.; Brabant, G.; Hesch, R. [Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, D-30623 Hannover (Germany); Sejnowski, T.J. [Howard Hughes Medical Institute and Computational Neurobiology Laboratory, The Salk Institute, San Diego, California 92186-5800 (United States)

    1996-06-01

    Pulsatile hormone secretion is observed in almost every hormonal system. The frequency of episodic hormone release ranges from approximately 10 to 100 pulses in 24 hours. This temporal mode of secretion is an important feature of intercellular information transfer in addition to a dose-response dependent regulation. It has been demonstrated in a number of experiments that changes in the temporal pattern of pulsatile hormone secretion specifically regulate cellular and organ function and structure. Recent evidence links osteoporosis, a disease characterized by loss of bone mass and structure, to changes in the dynamics of pulsatile parathyroid hormone (PTH) secretion. In our study we applied nonlinear and linear time series prediction to characterize the secretory dynamics of PTH in both healthy human subjects and patients with osteoporosis. Osteoporotic patients appear to lack periods of high predictability found in normal humans. In contrast to patients with osteoporosis patients with hyperparathyroidism, a condition which despite sometimes reduced bone mass has a preserved bone architecture, show periods of high predictability of PTH secretion. Using stochastic surrogate data sets which match certain statistical properties of the original time series significant nonlinear determinism could be found for the PTH time series of a group of healthy subjects. Using classical nonlinear analytical techniques we could demonstrate that the irregular pattern of pulsatile PTH secretion in healthy men exhibits characteristics of deterministic chaos. Pulsatile secretion of PTH in healthy subjects seems to be a first example of nonlinear determinism in an apparently irregular hormonal rhythm in human physiology. {copyright} {ital 1996 American Institute of Physics.}

  15. Genetics of Isolated Hypogonadotropic Hypogonadism: Role of GnRH Receptor and Other Genes

    Directory of Open Access Journals (Sweden)

    Karges Beate

    2012-01-01

    Full Text Available Hypothalamic gonadotropin releasing hormone (GnRH is a key player in normal puberty and sexual development and function. Genetic causes of isolated hypogonadotropic hypogonadism (IHH have been identified during the recent years affecting the synthesis, secretion, or action of GnRH. Developmental defects of GnRH neurons and the olfactory bulb are associated with hyposmia, rarely associated with the clinical phenotypes of synkinesia, cleft palate, ear anomalies, or choanal atresia, and may be due to mutations of KAL1, FGFR1/FGF8, PROKR2/PROK2, or CHD7. Impaired GnRH secretion in normosmic patients with IHH may be caused by deficient hypothalamic GPR54/KISS1, TACR3/TAC3, and leptinR/leptin signalling or mutations within the GNRH1 gene itself. Normosmic IHH is predominantly caused by inactivating mutations in the pituitary GnRH receptor inducing GnRH resistance, while mutations of the β-subunits of LH or FSH are very rare. Inheritance of GnRH deficiency may be oligogenic, explaining variable phenotypes. Future research should identify additional genes involved in the complex network of normal and disturbed puberty and reproduction.

  16. The stimulation of testosterone and LH secretion by synthetic GnRH ...

    African Journals Online (AJOL)

    The effects of GnRH stimulation on plasma testosterone and luteinizing hormone (LH) levels in Cape porcupine males were examined by analysing plasma collected before and after an intravenous injection of GnRH. In six mature males and one subadult, which were given an intravenous injection of 0,5 ml saline, levels of ...

  17. Low-dose add-back therapy during postoperative GnRH agonist treatment

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Tsai

    2016-02-01

    Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

  18. Specification of GnRH-1 neurons by antagonistic FGF and retinoic acid signaling.

    Science.gov (United States)

    Sabado, Virginie; Barraud, Perrine; Baker, Clare V H; Streit, Andrea

    2012-02-15

    A small population of neuroendocrine cells in the rostral hypothalamus and basal forebrain is the key regulator of vertebrate reproduction. They secrete gonadotropin-releasing hormone (GnRH-1), communicate with many areas of the brain and integrate multiple inputs to control gonad maturation, puberty and sexual behavior. In humans, disruption of the GnRH-1 system leads to hypogonadotropic gonadism and Kallmann syndrome. Unlike other neurons in the central nervous system, GnRH-1 neurons arise in the periphery, however their embryonic origin is controversial, and the molecular mechanisms that control their initial specification are not clear. Here, we provide evidence that in chick GnRH-1 neurons originate in the olfactory placode, where they are specified shortly after olfactory sensory neurons. FGF signaling is required and sufficient to induce GnRH-1 neurons, while retinoic acid represses their formation. Both pathways regulate and antagonize each other and our results suggest that the timing of signaling is critical for normal GnRH-1 neuron formation. While Kallmann's syndrome has generally been attributed to a failure of GnRH-1 neuron migration due to impaired FGF signaling, our findings suggest that in at least some Kallmann patients these neurons may never be specified. In addition, this study highlights the intimate embryonic relationship between GnRH-1 neurons and their targets and modulators in the adult. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics

    DEFF Research Database (Denmark)

    Muñoz, Manuel; Cruz, María; Humaidan, Peter

    2013-01-01

    OBJECTIVE: To explore if the GnRH analogue used for controlled ovarian stimulation (COS) and the ovulation triggering factor (GnRH agonist+hCG triggering versus GnRH antagonist+GnRH agonist triggering) affect embryo development and kinetics. STUDY DESIGN: In a retrospective cohort study...

  20. Long-term effects of GnRH agonists on fertility and behaviour

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin

    2017-01-01

    This review aimed to summarize the present knowledge about the effects of GnRH agonist slow-release implants (GnRH A-SRI) on fertility and behaviour in male and female dogs and cats with special focus on deslorelin. Following an initial stimulation of gonadotropin and testosterone secretion...... possibly associated with an improved semen quality, GnRH A-SRI induce long-term depression of fertility in male dogs and cats with, however, a large individual variation in onset and duration of efficacy especially in cats. The GnRH A-SRI furthermore interfere with testosterone-dependent/affected behaviour......; a significant positive effect in reducing sexual behaviour and libido, hypersexuality, intermale dominance and excessive territorial urine marking has been described. Rates of improvement of the respective behaviour are comparable to those after surgical castration, making GnRH A-SRI a valuable option...

  1. Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

    Directory of Open Access Journals (Sweden)

    Abbas Aflatoonian

    2017-08-01

    Full Text Available Background: Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART. Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards. Objective: The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF outcomes. Materials and Methods: This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30, delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30 treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results: Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups. Conclusion: There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

  2. Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release.

    Science.gov (United States)

    Satarkar, Nitin S; Hilt, J Zach

    2008-09-24

    Hydrogel nanocomposites are novel macromolecular biomaterials that promise to impact various applications in medical and pharmaceutical fields. In this paper, magnetic nanocomposites of temperature responsive hydrogels were used to illustrate remote controlled (RC) drug delivery. A high frequency alternating magnetic field (AMF) was used to trigger the on-demand pulsatile drug release from the nanocomposites. Nanocomposites were synthesized by incorporation of superparamagnetic Fe(3)O(4) particles in negative temperature sensitive poly (N-isopropylacrylamide) hydrogels. Pulses of AMF were applied to the nanocomposites and the kinetics of collapse and recovery were characterized. Application of AMF resulted in uniform heating within the nanocomposites leading to accelerated collapse and squeezing out large amounts of imbibed drug (release at a faster rate). Remote controlled pulsatile drug release was characterized for different drugs as well as for different ON-OFF durations of the AMF.

  3. Tissue Pulsatility Imaging of Cerebral Vasoreactivity during Hyperventilation

    Science.gov (United States)

    Kucewicz, John C.; Dunmire, Barbrina; Giardino, Nicholas D.; Leotta, Daniel F.; Paun, Marla; Dager, Stephen R.; Beach, Kirk W.

    2008-01-01

    Tissue Pulsatility Imaging (TPI) is an ultrasonic technique that is being developed at the University of Washington to measure tissue displacement or strain due to blood flow over the cardiac and respiratory cycles. This technique is based in principle on plethysmography, an older non-ultrasound technology for measuring expansion of a whole limb or body part due to perfusion. TPI adapts tissue Doppler signal processing methods to measure the “plethysmographic” signal from hundreds or thousands of sample volumes in an ultrasound image plane. This paper presents a feasibility study to determine if TPI can be used to assess cerebral vasoreactivity. Ultrasound data were collected transcranially through the temporal acoustic window from four subjects before, during, and after voluntary hyperventilation. In each subject, decreases in tissue pulsatility during hyperventilation were observed that were statistically correlated with the subject’s end-tidal CO2 measurements. PMID:18336991

  4. Dynamic evolution of the GnRH receptor gene family in vertebrates.

    Science.gov (United States)

    Williams, Barry L; Akazome, Yasuhisa; Oka, Yoshitaka; Eisthen, Heather L

    2014-10-25

    Elucidating the mechanisms underlying coevolution of ligands and receptors is an important challenge in molecular evolutionary biology. Peptide hormones and their receptors are excellent models for such efforts, given the relative ease of examining evolutionary changes in genes encoding for both molecules. Most vertebrates possess multiple genes for both the decapeptide gonadotropin releasing hormone (GnRH) and for the GnRH receptor. The evolutionary history of the receptor family, including ancestral copy number and timing of duplications and deletions, has been the subject of controversy. We report here for the first time sequences of three distinct GnRH receptor genes in salamanders (axolotls, Ambystoma mexicanum), which are orthologous to three GnRH receptors from ranid frogs. To understand the origin of these genes within the larger evolutionary context of the gene family, we performed phylogenetic analyses and probabilistic protein homology searches of GnRH receptor genes in vertebrates and their near relatives. Our analyses revealed four points that alter previous views about the evolution of the GnRH receptor gene family. First, the "mammalian" pituitary type GnRH receptor, which is the sole GnRH receptor in humans and previously presumed to be highly derived because it lacks the cytoplasmic C-terminal domain typical of most G-protein coupled receptors, is actually an ancient gene that originated in the common ancestor of jawed vertebrates (Gnathostomata). Second, unlike previous studies, we classify vertebrate GnRH receptors into five subfamilies. Third, the order of subfamily origins is the inverse of previous proposed models. Fourth, the number of GnRH receptor genes has been dynamic in vertebrates and their ancestors, with multiple duplications and losses. Our results provide a novel evolutionary framework for generating hypotheses concerning the functional importance of structural characteristics of vertebrate GnRH receptors. We show that five

  5. Pulsatility role in cylinder flow dynamics at low Reynolds number

    KAUST Repository

    Qamar, Adnan

    2012-01-01

    We present dynamics of pulsatile flow past a stationary cylinder characterized by three non-dimensional parameters: the Reynolds number (Re), non-dimensional amplitude (A) of the pulsatile flow velocity, and Keulegan-Carpenter number (KC = Uo/Dωc). This work is motivated by the development of total artificial lungs (TAL) device, which is envisioned to provide ambulatory support to patients. Results are presented for 0.2 ≤ A ≤ 0.6 and 0.57 ≤ KC ≤ 2 at Re = 5 and 10, which correspond to the operating range of TAL. Two distinct fluid regimes are identified. In both regimes, the size of the separated zone is much greater than the uniform flow case, the onset of separation is function of KC, and the separation vortex collapses rapidly during the last fraction of the pulsatile cycle. The vortex size is independent of KC, but with an exponential dependency on A. In regime I, the separation point remains attached to the cylinder surface. In regime II, the separation point migrates upstream of the cylinder. Two distinct vortex collapse mechanisms are observed. For A < 0.4 and all KC and Re values, collapse occurs on the cylinder surface, whereas for A > 0.4 the separation vortex detaches from the cylinder surface and collapses at a certain distance downstream of the cylinder. The average drag coefficient is found to be independent of A and KC, and depends only on Re. However, for A > 0.4, for a fraction of the pulsatile cycle, the instantaneous drag coefficient is negative indicating a thrust production. © 2012 American Institute of Physics.

  6. Pulsatile blood flow, shear force, energy dissipation and Murray's Law

    Directory of Open Access Journals (Sweden)

    Bengtsson Hans-Uno

    2006-08-01

    Full Text Available Abstract Background Murray's Law states that, when a parent blood vessel branches into daughter vessels, the cube of the radius of the parent vessel is equal to the sum of the cubes of the radii of daughter blood vessels. Murray derived this law by defining a cost function that is the sum of the energy cost of the blood in a vessel and the energy cost of pumping blood through the vessel. The cost is minimized when vessel radii are consistent with Murray's Law. This law has also been derived from the hypothesis that the shear force of moving blood on the inner walls of vessels is constant throughout the vascular system. However, this derivation, like Murray's earlier derivation, is based on the assumption of constant blood flow. Methods To determine the implications of the constant shear force hypothesis and to extend Murray's energy cost minimization to the pulsatile arterial system, a model of pulsatile flow in an elastic tube is analyzed. A new and exact solution for flow velocity, blood flow rate and shear force is derived. Results For medium and small arteries with pulsatile flow, Murray's energy minimization leads to Murray's Law. Furthermore, the hypothesis that the maximum shear force during the cycle of pulsatile flow is constant throughout the arterial system implies that Murray's Law is approximately true. The approximation is good for all but the largest vessels (aorta and its major branches of the arterial system. Conclusion A cellular mechanism that senses shear force at the inner wall of a blood vessel and triggers remodeling that increases the circumference of the wall when a shear force threshold is exceeded would result in the observed scaling of vessel radii described by Murray's Law.

  7. Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol

    DEFF Research Database (Denmark)

    Toftager, M.; Bogstad, J; Bryndorf, T

    2016-01-01

    subjects who started gonadotrophin stimulation were included. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of severe OHSS [5.1% (27/528) versus 8.9% (44/495) (difference in proportion percentage point (Δpp) = -3.8pp; 95% CI: -7.1 to -0.4; P = 0.02)] and moderate OHSS [10.2% (54/528) versus 15.6% (77...... gonadotrophin stimulation and per embryo transfer were all similar in the two groups. LIMITATIONS, REASONS FOR CAUTION: A possible limitation is the duration of the trial, with new methods, such as 'freeze all' and 'GnRH agonist triggering', being developed during the trial, the new methods were sought avoided......, however a total number of 32 women had 'freeze all' and 'GnRH agonist triggering' was performed in three cases. Ultrasonic measurements were performed by different physicians and inter-observer bias may be present. Measures of anti-Mullerian hormone and antral follicle count, to estimate ovarian reserve...

  8. Pulsatile flow conditioning of three-dimensional bioengineered cardiac ventricle.

    Science.gov (United States)

    Patel, Nikita M; Birla, Ravi K

    2016-12-05

    Current physical stimuli mechanical stretch bioreactor studies focus on conditioning planar and/or tubular engineered cardiac constructs. The current 3D bioreactor models in cardiac tissue engineering use differential pressure loading for structural support as opposed to conditioning. The development of the pulsatile flow conditioned ventricle (PFCV) provides a 3D mechanical stretch conditioning method to generate pump function in the engineered cardiac left ventricle. The study utilizes a chitosan bioengineered open ventricle scaffold, to produce the in vitro PFCV model. PFCV were fabricated by wrapping the outer scaffold surface with a 3D fibrin gel artificial heart muscle patch, followed by pulsatile flow conditioning for 20 h. The average contractile frequency was 57 bpm. The average pressure generated, under maintained flow, post-conditioning, was 3.1633 mmHg. The average biopotential output was 0.4881 mV. Histologically, the PFCV displayed a more disseminated presence of intercellular interactions and sarcomeric organization. The results of this study clearly demonstrate the effectiveness of pulsatile flow conditioning to improve the function of our engineered left ventricle.

  9. Effects of pulsatile flow on cultured vascular endothelial cell morphology.

    Science.gov (United States)

    Helmlinger, G; Geiger, R V; Schreck, S; Nerem, R M

    1991-05-01

    Endothelial cells (EC) appear to adapt their morphology and function to the in vivo hemodynamic environment in which they reside. In vitro experiments indicate that similar alterations occur for cultured EC exposed to a laminar steady-state flow-induced shear stress. However, in vivo EC are exposed to a pulsatile flow environment; thus, in this investigation, the influence of pulsatile flow on cell shape and orientation and on actin microfilament localization in confluent bovine aortic endothelial cell (BAEC) monolayers was studied using a 1-Hz nonreversing sinusoidal shear stress of 40 +/- 20 dynes/cm2 (type I), 1-Hz reversing sinusoidal shear stresses of 20 +/- 40 and 10 +/- 15 dynes/cm2 (type II), and 1-Hz oscillatory shear stresses of 0 +/- 20 and 0 +/- 40 dynes/cm2 (type III). The results show that in a type I nonreversing flow, cell shape changed less rapidly, but cells took on a more elongated shape than their steady flow controls long-term. For low-amplitude type II reversing flow, BAECs changed less rapidly in shape and were always less elongated than their steady controls; however, for high amplitude reversal, BAECs did not stay attached for more than 24 hours. For type III oscillatory flows, BAEC cell shape remained polygonal as in static culture and did not exhibit actin stress fibers, such as occurred in all other flows. These results demonstrate that EC can discriminate between different types of pulsatile flow environments.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Pulsatile entrance flow in curved pipes: effect of various parameters

    Science.gov (United States)

    Sumida, Masaru

    2007-12-01

    This paper presents the results of an experimental study on the developing pulsatile flow in curved pipes with a long, straight pipe upstream. In order to examine the dependence of flow-field development on the governing parameters, LDV measurements were conducted systematically for six cases of flow, where the Womersley number α was varied from 5.5 to 18, the mean Dean number D m was 200 and 300, the flow rate ratio η was 0.5 and 1, and the curvature radius ratio Rc was 10 and 30. Peculiar flow phenomena, such as flow reversal for all values of α and a depression in the axial velocity profile for α = 10, were analyzed by decomposing the axial velocity into a time-mean and a varying component, as well as by obtaining the bias of their profiles. The velocity distributions abruptly change with the phase at turn angles Ω of 15 30°, corresponding to the nondimensional axial length z' ≅ 1 2 from the bend entrance, and their development along the pipe axis is the most complicated for the flow at a moderate α of 10 and large η of 1. The entrance length in the case of pulsatile flow is shorter than that for steady flow with the same flow rate as the maximum pulsatile flow rate.

  11. Effect of pulsatile swirling flow on stenosed arterial blood flow.

    Science.gov (United States)

    Ha, Hojin; Lee, Sang Joon

    2014-09-01

    The existence of swirling flow phenomena is frequently observed in arterial vessels, but information on the fluid-dynamic roles of swirling flow is still lacking. In this study, the effects of pulsatile swirling inlet flows with various swirling intensities on the flow field in a stenosis model are experimentally investigated using a particle image velocimetry velocity field measurement technique. A pulsatile pump provides cyclic pulsating inlet flow and spiral inserts with two different helical pitches (10D and 10/3D) induce swirling flow in the stenosed channel. Results show that the pulsatile swirling flow has various beneficial effects by reducing the negative wall shear stress, the oscillatory shear index, and the flow reverse coefficient at the post-stenosis channel. Temporal variations of vorticity fields show that the short propagation length of the jet flow and the early breakout of turbulent flow are initiated as the swirling flow disturbs the symmetric development of the shear layer. In addition, the overall energy dissipation rate of the flow is suppressed by the swirling component of the flow. The results will be helpful for elucidating the hemodynamic characteristics of atherosclerosis and discovering better diagnostic procedures and clinical treatments. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

  12. GnRH Protein Levels in Atrazine-Treated Axolotls (Ambystoma mexicanum

    Directory of Open Access Journals (Sweden)

    Sarah Leupen

    2008-01-01

    Full Text Available Atrazine is the most widely used agricultural herbicide in the United States and a known endocrine disruptor. In amphibians, it has been shown to cause gonadal malformations, feminization of males, behavioral changes, and immune suppression; however, its mechanism ofaction is unknown. We hypothesized that atrazine reduces the production of gonadotropin releasing hormone (GnRH in the hypothalamus. Axolotls (Ambystoma mexicanum were exposed to atrazine, 10-8 M ß-estradiol-3-benzoate, or no treatment and were sacrificed at 6, 8, and 10 months of age. GnRH neurons were labeled using immunocytochemistry, and labeled neurons were then counted using confocal microscopy. Although no significant difference wasfound in the total number of GnRH neurons, ectopic GnRH expression was seen in some brains. A significant negative correlation was found between presence of ectopic GnRH and number of normal GnRH neurons. Atrazine-treated animals were more likely than control or estrogentreated animals to have ectopic GnRH expression. The data implicate a central site of action of atrazine.

  13. Characterization of Gnrh/Gnih elements in the olfacto-retinal system and ovary during zebrafish ovarian maturation.

    Science.gov (United States)

    Corchuelo, Sheryll; Martinez, Emanuel R M; Butzge, Arno J; Doretto, Lucas B; Ricci, Juliana M B; Valentin, Fernanda N; Nakaghi, Laura S O; Somoza, Gustavo M; Nóbrega, Rafael H

    2017-07-15

    Gonadotropin releasing hormone (GnRH) is one of the key players of brain-pituitary-gonad axis, exerting overall control over vertebrate reproduction. In zebrafish, two variants were characterized and named as Gnrh2 and Gnrh3. In this species, Gnrh3, the hypohysiotropic form, is expressed by neurons of the olfactory-retinal system, where it is related with food detection, intra/interspecific recognition, visual acuity and retinal processing modulation. Previous studies have reported the presence of Gnrh receptors in the zebrafish retina, but not yet in the zebrafish olfactory epithelium. The current study analyzed the presence of gnrh2 and gnrh3, their receptors (gnrhr 1,2,3 and 4) and gnih (gonadotropin inhibitory hormone) transcripts, as well as the Gnrh3 protein in the olfactory epithelium (OE), olfactory bulb (OB), retina and ovary during zebrafish ovarian maturation. We found an increase of gnrh receptors transcripts in the OE at the final stages of ovarian maturation. In the OE, Gnrh3 protein was detected in the olfactory receptor neurons cilia and in the olfactory nerve fibers. Interestingly, in the OB, we found an inverse expression pattern between gnih and gnrh3. In the retina, gnrhr4 mRNA was found in the nuclei of amacrine, bipolar, and ganglion cells next to Gnrh3 positive fibers. In the ovary, gnrh3, gnrhr2 and gnrhr4 transcripts were found in perinucleolar oocytes, while gnih in oocytes at the cortical alveolus stage. Our results suggested that Gnrh/Gnih elements are involved in the neuromodulation of the sensorial system particularly at the final stages of maturation, playing also a paracrine role in the ovary. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Coupling the Guyton model to pulsatile ventricles using a multiresolution modelling environment.

    OpenAIRE

    Le Rolle, Virginie; Ojeda, David; Madeleine, Raphael; Carrault, Guy; Hernández, Alfredo,

    2010-01-01

    International audience; In this paper, we propose the substitution of the original, non-pulsatile cardiac sub-model of the Guyton model by an elastance-based pulsatile model of the heart, including interventricular interaction through the septum. Parameters of this cardiac model were identified by comparing the simulations obtained from the original Guyton model with those obtained from the proposed integrated, pulsatile model, during the 5 minutes simulation of a sudden severe muscle exercis...

  15. Amoxicillin Pulsatile MiddleBrook: APC 111, APC-111, PULSYS-Enhanced Amoxicillin

    National Research Council Canada - National Science Library

    Adis International Limited

    2007-01-01

    MiddleBrook Pharmaceuticals (formerly Advancis Pharmaceutical) is developing an improved version of amoxicillin using its pulsatile oral drug delivery technology, called PULSYS™. Amoxicillin PULSYS...

  16. KNDy (Kisspeptin/Neurokinin B/Dynorphin) Neurons Are Activated during Both Pulsatile and Surge Secretion of LH in the Ewe

    Science.gov (United States)

    Merkley, Christina M.; Porter, Katrina L.; Coolen, Lique M.; Hileman, Stanley M.; Billings, Heather J.; Drews, Sara; Goodman, Robert L.

    2012-01-01

    KNDy (kisspeptin/neurokinin B/dynorphin) neurons of the arcuate nucleus (ARC) appear to mediate the negative feedback actions of estradiol and are thought to be key regulators of pulsatile LH secretion. In the ewe, KNDy neurons may also be involved with the positive feedback actions of estradiol (E2) to induce the LH surge, but the role of kisspeptin neurons in the preoptic area (POA) remains unclear. The goal of this study was to identify which population(s) of kisspeptin neurons is (are) activated during the LH surge and in response to the removal of E2-negative feedback, using Fos as an index of neuronal activation. Dual-label immunocytochemistry for kisspeptin and Fos was performed on sections containing the ARC and POA from ewes during the luteal phase of the estrous cycle, or before or after the onset of the LH surge (experiment 1), and from ovary-intact, short-term (24 h) and long-term (>30 d) ovariectomized (OVX) ewes in anestrus (experiment 2). The percentage of kisspeptin neurons expressing Fos in both the ARC and POA was significantly higher during the LH surge. In contrast, the percentage of kisspeptin/Fos colocalization was significantly increased in the ARC, but not POA, after both short- and long-term E2 withdrawal. Thus, POA kisspeptin neurons in the sheep are activated during, and appear to contribute to, E2-positive feedback, whereas ARC kisspeptin (KNDy) neurons are activated during both surge and pulsatile modes of secretion and likely play a role in mediating both positive and negative feedback actions of E2 on GnRH secretion in the ewe. PMID:22989631

  17. Mathematical modeling of the GnRH pulse and surge generator

    CERN Document Server

    Clement, Frederique

    2007-01-01

    We propose a mathematical model allowing for the alternating pulse and surge pattern of GnRH (Gonadotropin Releasing Hormone) secretion. The model is based on the coupling between two systems running on different time scales. The faster system corresponds to the average activity of GnRH neurons, while the slower one corresponds to the average activity of regulatory neurons. The analysis of the slow/fast dynamics exhibited within and between both systems allows to explain the different patterns (slow oscillations, fast oscillations and periodical surge) of GnRH secretion. Specifications on the model parameter values are derived from physiological knowledge in terms of amplitude, frequency and plateau length of oscillations. The behavior of the model is finally illustrated by numerical simulations reproducing natural ovarian cycles and either direct or indirect actions of ovarian steroids on GnRH secretion.

  18. Mental distress and personality in women undergoing GnRH agonist versus GnRH antagonist protocols for assisted reproductive technology

    DEFF Research Database (Denmark)

    Stenbæk, D. S.; Toftager, M.; Hjordt, L. V.

    2015-01-01

    STUDY QUESTION: Do mental distress and mood fluctuations in women undergoing GnRH agonist and GnRH antagonist protocols for assisted reproductive technology (ART) differ depending on protocol and the personality trait, neuroticism? SUMMARY ANSWER: ART treatment did not induce elevated levels...... of mental distress in either GnRH antagonist or agonist protocols but neuroticism was positively associated with increased mental distress, independent of protocols. WHAT IS KNOWN ALREADY: ART treatment may increase mental distress by mechanisms linked to sex hormone fluctuations. General psychological......-reported the Profile of Mood States, the Perceived Stress Scale, the Symptom Checklist-92-Revised, and the Major Depression Inventory questionnaires, at baseline, at ART cycle day 35, on the day of oocyte pick-up, and on the day of hCG testing. Also, a series of Profile of Mood States were reported daily during...

  19. In vitro regulation of LH biosynthesis and release by GnRH and estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Ramey, J.W.

    1986-01-01

    Anterior pituitaries were taken from female rats at random stages of the estrous cycle, enzymatically dispersed, and cultured for 48h in steroid-free ..cap alpha..-modified Eagles medium followed by 24h in fresh medium +/- estradiol (E/sub 2/). The pituitary cells were then incubated in fresh medium containing radiolabeled precursors +/- gonadotropin releasing hormone (GnRH). Radioactive precursor incorporation into LH was determined by immuno-precipitation. The dose-dependent effects of E/sub 2/(10/sup -11/ to 10/sup -8/M) on /sup 3/H-glucosamine (/sup 3/H-Gln) and /sup 35/S-methionine (/sup 35/S-Met) incorporation into LH +/- 1 nM GnRH (4h) were investigated. GnRH (10/sup -9/M) and E/sub 2/ (all doses) significantly increased total /sup 3/H-Gln LH. Moreover, E/sub 2/ at 10/sup -9/M and 10/sup -8/M significantly enhanced GnRH stimulated LH glycosylation. In contrast, addition of GnRH and/or E/sub 2/ did not significantly increase /sup 35/S-Met incorporation into LH over a 4h period. The effects of various GnRH concentrations (10/sup -11/ to 10/sup -9/M; 8h) +/- E/sub 2/ (0.05 nM) on /sup 3/H-Gln LH and /sup 35/S-Met LH production were also investigated. In the absence of E/sub 2/, only 10/sup -9/M GnRH was effective in increasing total /sup 3/H-Gln LH and /sup 35/S-Met LH synthesis. However, in the presence of E/sub 2/, all concentrations of GnRH stimulated LH synthesis with /sup 3/H-Gln LH production responding in a dose related manner whereas /sup 35/S-Met LH production was maximally stimulated at all doses of GnRH. In the final series of experiments, pituitary cells previously exposed to estradiol were incubated for 4 h in normal calcium or low calcium medium containing /sup 3/H-Gln or /sup 35/S-Met +/- GnRH. Removal of extracellular calcium completely inhibited GnRH stimulated /sup 3/H-Gln LH and /sup 35/S-Met LH production.

  20. An Optimization Formulation for Characterization of Pulsatile Cortisol Secretion

    Directory of Open Access Journals (Sweden)

    Rose Taj Faghih

    2015-08-01

    Full Text Available Cortisol is released to relay information to cells to regulate metabolism and reaction to stress and inflammation. In particular, cortisol is released in the form of pulsatile signals. This low-energy method of signaling seems to be more efficient than continuous signaling. We hypothesize that there is a controller in the anterior pituitary that leads to pulsatile release of cortisol, and propose a mathematical formulation for such controller, which leads to impulse control as opposed to continuous control. We postulate that this controller is minimizing the number of secretory events that result in cortisol secretion, which is a way of minimizing the energy required for cortisol secretion; this controller maintains the blood cortisol levels within a specific circadian range while complying with the first order dynamics underlying cortisol secretion. We use an l0-norm cost function for this controller, and solve a reweighed l1-norm minimization algorithm for obtaining the solution to this optimization problem. We use 4 examples to illustrate the performance of this approach: (i a toy problem that achieves impulse control, (ii two examples that achieve physiologically plausible pulsatile cortisol release, (iii an example where the number of pulses is not within the physiologically plausible range for healthy subjects while the cortisol levels are within the desired range. This novel approach results in impulse control where the impulses and the obtained blood cortisol levels have a circadian rhythm and an ultradian rhythm that are in agreement with the known physiology of cortisol secretion. The proposed formulation is a first step in developing intermittent controllers for curing cortisol deficiency. This type of bio-inspired pulse controllers can be employed for designing non-continuous controllers in brain-machine interface design for neuroscience applications.

  1. Highly immunogenic and fully synthetic peptide-carrier constructs targetting GnRH

    DEFF Research Database (Denmark)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Turkstra, J.A.

    1999-01-01

    using a tandem GnRH peptide as a branched polylysine construct, a lipo-thioester, a lipo-amide or a KLH conjugate in CFA, and the lipoamide peptide in an immuno-stimulating complex (ISCOM). We found the lipo-thioester and the branched polylysine constructs to be the most effective carrier molecules...... for the induction of antibodies against GnRH and immunocastration of pigs....

  2. Spaying-induced coat changes: the role of gonadotropins, GnRH and GnRH treatment on the hair cycle of female dogs.

    Science.gov (United States)

    Reichler, Iris Margaret; Welle, Monika; Eckrich, Christine; Sattler, Ursula; Barth, Andrea; Hubler, Madeleine; Nett-Mettler, Claudia S; Jöchle, Wolfgang; Arnold, Susi

    2008-04-01

    Although spaying can result in qualitative hair coat changes in dogs, the influence of spaying on the hair growth cycle has never been described. The study aims were to examine the effect of spaying and gonadotropin-releasing hormone (GnRH) treatment on canine hair coat, cycle stages of hair follicles, plasma gonadotropin concentrations and mRNA transcription of luteinizing hormone (LH) and GnRH receptors in hair follicles. Fifteen female dogs were examined before and 1 year after spaying and 24 spayed dogs before and after GnRH treatment. Spaying resulted in increased plasma gonadotropin concentrations and increased anagen : telogen ratio of hair follicles, but only 20% of the dogs developed coat changes. No differences were found in mRNA transcription of LH and GnRH receptors. GnRH treatment resulted in reduced plasma gonadotropin concentrations and improvement of coat changes in 79% of patients. This was associated with an increase in catagen hair follicles without changes in the anagen : telogen ratio. The present study demonstrated that spaying had an effect on the anagen : telogen ratio of hair follicles. Spaying-induced coat changes did not correlate with the anagen : telogen ratio. GnRH treatment reduced gonadotropin concentrations and reversed coat changes in some dogs, but had no effect on the hair growth cycle other than increasing the number of catagen hair follicles. A weak positive correlation between the plasma LH concentration and the anagen : telogen ratio was noted; however, our data did not suggest a direct receptor-mediated hormonal effect on the hair follicle. The present study did not identify the pathomechanism of spaying-induced coat changes.

  3. Controle sobre GnRH durante o anestro pós-parto em bovinos GnRH control during bovine postpartum anestrous

    Directory of Open Access Journals (Sweden)

    João Francisco Coelho de Oliveira

    2010-12-01

    Full Text Available O pós-parto em bovinos é caracterizado como um momento em que as fêmeas bovinas não ovulam, principalmente devido a uma inadequada liberação de gonadotrofinas. Os conceitos e os mecanismos regulatórios do hormônio liberador de gonadotrofinas (GnRH têm sido descritos isoladamente. Esta revisão aborda a influência da nutrição e amamentação, com enfoque na regulação do GnRH, e fornece conceitos atuais do controle neuroendocrinológico da secreção de GnRH durante o pós-parto em bovinos. Conhecimentos atuais das funções do hormônio inibitório de gonadotrofinas (GnIH, da leptina, dos estrógenos, da kisspeptina e da adiponectina, bem como suas complexas inter-relações durante este período estão detalhados para melhor entendimento do assunto.The bovine postpartum period is characterized as a moment when the ovulation is suppressed, mainly in consequence of insufficient release of gonadotropins. Concepts and regulatory mechanisms of gonadotropin-releasing hormone (GnRH had been described independently. This review covers the influence of nutrition and suckling with emphasis on GnRH regulation, and provides up to date concepts of neuroendocrine control of GnRH secretion during postpartum in cattle. Current knowledge of gonadotropin-inhibitory hormone (GnIH, leptin, estrogens and kisspeptin during this period are presented in order to provide a better understanding of the subject.

  4. Dependence of fertility on kisspeptin-Gpr54 signaling at the GnRH neuron.

    Science.gov (United States)

    Kirilov, Milen; Clarkson, Jenny; Liu, Xinhuai; Roa, Juan; Campos, Pauline; Porteous, Rob; Schütz, Günther; Herbison, Allan E

    2013-01-01

    Signaling between kisspeptin and its receptor, G-protein-coupled receptor 54 (Gpr54), is now recognized as being essential for normal fertility. However, the key cellular location of kisspeptin-Gpr54 signaling is unknown. Here we create a mouse with a GnRH neuron-specific deletion of Gpr54 to assess the role of gonadotropin-releasing hormone (GnRH) neurons. Mutant mice are infertile, fail to go through puberty and exhibit markedly reduced gonadal size and follicle-stimulating hormone levels alongside GnRH neurons that are unresponsive to kisspeptin. In an attempt to rescue the infertile phenotype of global Gpr54⁻/⁻ mutants, we use BAC transgenesis to target Gpr54 to the GnRH neurons. This results in mice with normal puberty onset, estrous cyclicity, fecundity and a recovery of kisspeptin's stimulatory action upon GnRH neurons. Using complimentary cell-specific knockout and knockin approaches we demonstrate here that the GnRH neuron is the key site of kisspeptin-Gpr54 signaling for fertility.

  5. Evaluation of GnRH analogue testing in diagnosis and management of children with pubertal disorders

    Directory of Open Access Journals (Sweden)

    Hemchand K Prasad

    2012-01-01

    Full Text Available Context: Gonadotrophin releasing hormone (GnRH stimulation test is pivotal in the assessment of children with pubertal disorders. However, lack of availability and high cost often result in the test falling into disfavor. We routinely use the GnRH analogue stimulation test as an alternative at our center. Aim: To present the data on children with endocrine disorders who underwent GnRH agonist stimulation test in pediatric endocrine clinic of a tertiary care referral hospital. Setting and Design: Pediatric endocrine clinic of a tertiary care referral hospital. Retrospective analysis of case records. Materials and Methods: The details pertaining to clinical and radiological parameters and hormonal tests were retrieved from case records of 15 children who underwent GnRH agonist stimulation test from May 2010 to April 2011. Results: Indications for testing with GnRH analogue were evaluation of delayed puberty, diagnosis of precocious puberty, assessment of hormonal suppression in treatment of precocious puberty and micropenis in two, nine, three and one cases, respectively. The results of the test and clinical and radiological parameters were in concordance. The test was also crucial in diagnosing the onset of central precocious puberty in two children with congenital adrenal hyperplasia. Conclusion: GnRH agonist test is a convenient, safe test that can be performed on an out-patient basis and can help the clinicians in the correct diagnosis and appropriate treatment of various puberty-related disorders.

  6. Reaction of cows ovaries to GnRH administration in different estrus cycle stages

    Directory of Open Access Journals (Sweden)

    Casiana Ciolac Șipețan

    2017-05-01

    Full Text Available Administration of GnRH in the luteal phase of estrous in dairy cows induces an increase of LH levels, with the modification of the growth waves of the ovarian follicles. GnRH induces ovulation or atresia of the dominant follicle and the recruitment of a new wave of follicular growth. The GnRH administration in the luteal phase of the estrous cycle induces growth waves synchronization of ovarian follicles, so that, a new wave of follicles started to grow at 5-6 days after administration. In our experiments, we administered 2ml Ovarelin (100 mcg GnRH, to three groups of cows (116 cows: in early luteal phase of the estrous cycle (days 4-5, in the middle of luteal phase (days 9-12, and late luteal phase (days 15-16. The rates of cows standing heat were 91.66% when GnRH was administered in early luteal phase, 95.22% when was administrated in the middle of luteal phase, and 73.68% in late luteal phase GnRH administration. After artificial insemination, the conception rates were 48.48% in early luteal phase, 52.5% at middle luteal phase and 46.42% in the late luteal phase of the estrous cycle.

  7. Immersed boundary method for pulsatile transitional flow in realistic cerebral aneurysms

    NARCIS (Netherlands)

    Mikhal, Julia Olegivna; Geurts, Bernardus J.

    2014-01-01

    We adopt a volume penalizing immersed boundary method for the simulation of pulsatile blood flow inside cerebral aneurysms. We show that the flow undergoes a transition from an orderly state at low physiological Reynolds numbers, in which the pulsatile forcing is closely followed in time, to a

  8. Pulsatile flow in a coronary artery using multiphase kinetic theory.

    Science.gov (United States)

    Huang, Jing; Lyczkowski, Robert W; Gidaspow, Dimitri

    2009-04-16

    Pulsatile flow in a model of a right coronary artery (RCA) was previously modeled as a single-phase fluid and as a two-phase fluid using experimental rheological data for blood as a function of hematocrit and shear rate. Here we present a multiphase kinetic theory model which has been shown to compute correctly the viscosity of red blood cells (RBCs) and their migration away from vessel walls: the Fahraeus-Lindqvist effect. The computed RBC viscosity decreases with shear rate and vessel size, consistent with measurements. The pulsatile computations were performed using a typical cardiac waveform until a limit cycle was well established. The RBC volume fractions, shear stresses, shear stress gradients, granular temperatures, viscosities, and phase velocities varied with time and position during each cardiac cycle. Steady-state computations were also performed and were found to compare well with time-averaged transient results. The wall shear stress and wall shear stress gradients (both spatial and temporal) were found to be highest on the inside area of maximum curvature. Potential atherosclerosis sites are identified using these computational results.

  9. Flow characteristics around a deformable stenosis under pulsatile flow condition

    Science.gov (United States)

    Choi, Woorak; Park, Jun Hong; Byeon, Hyeokjun; Lee, Sang Joon

    2018-01-01

    A specific portion of a vulnerable stenosis is deformed periodically under a pulsatile blood flow condition. Detailed analysis of such deformable stenosis is important because stenotic deformation can increase the likelihood of rupture, which may lead to sudden cardiac death or stroke. Various diagnostic indices have been developed for a nondeformable stenosis by using flow characteristics and resultant pressure drop across the stenosis. However, the effects of the stenotic deformation on the flow characteristics remain poorly understood. In this study, the flows around a deformable stenosis model and two different rigid stenosis models were investigated under a pulsatile flow condition. Particle image velocimetry was employed to measure flow structures around the three stenosis models. The deformable stenosis model was deformed to achieve high geometrical slope and height when the flow rate was increased. The deformation of the stenotic shape enhanced jet deflection toward the opposite vessel wall of the stenosis. The jet deflection in the deformable model increased the rate of jet velocity and turbulent kinetic energy (TKE) production as compared with those in the rigid models. The effect of stenotic deformation on the pulsating waveform related with the pressure drop was analyzed using the TKE production rate. The deformable stenosis model exhibited a phase delay of the peak point in the waveform. These results revealed the potential use of pressure drop waveform as a diagnostic index for deformable stenosis.

  10. Prediction and control of neural responses to pulsatile electrical stimulation

    Science.gov (United States)

    Campbell, Luke J.; Sly, David James; O'Leary, Stephen John

    2012-04-01

    This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s-1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s-1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

  11. Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

    Directory of Open Access Journals (Sweden)

    Guo S

    2017-03-01

    Full Text Available Song Guo,1,* Xiaowei Lu,1,* Ruihuan Gu,2 Di Zhang,3 Yijuan Sun,2 Yun Feng1 1Department of Obstetrics and Gynecology, Reproductive Medicine Center, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Gynecology, Shanghai Ji Ai Genetics & In Vitro Fertilization Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Gynecology and Obstetrics, Jinan Military General Hospital, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Adenomyosis is a common, benign gynecological condition of the female reproductive tract characterized by heavy menstrual bleeding and dysmenorrhea. Gonadotropin-releasing hormone (GnRH agonists are one of the medications used in adenomyosis treatment; however, their underlying mechanisms are poorly understood. Moreover, it is difficult to obtain endometrial samples from women undergoing such treatment. To overcome this, we generated an adenomyosis mouse model, which we treated with an GnRH agonist to determine its effect on pregnancy outcomes. We also analyzed endometrial gene expression following GnRH agonist treatment to determine the mechanisms that may affect pregnancy outcome in individuals with adenomyosis.Methods: Neonatal female mice were divided into a control group, an untreated adenomyosis group, and an adenomyosis group treated with a GnRH agonist (n=6 each. The pregnancy outcome was observed and compared among the groups. Then, three randomly chosen transcriptomes from endometrial tissues from day 4 of pregnancy were analyzed between the adenomyosis group and the GnRH agonist treatment group by RNA sequencing and quantitative reverse transcription polymerase chain reaction (PCR.Results: The litter size was significantly smaller in the adenomyosis group than in the control group (7±0.28 vs 11±0.26; P<0.05. However, the average live litter

  12. Fluid-structure interaction for nonlinear response of shells conveying pulsatile flow

    Science.gov (United States)

    Tubaldi, Eleonora; Amabili, Marco; Païdoussis, Michael P.

    2016-06-01

    Circular cylindrical shells with flexible boundary conditions conveying pulsatile flow and subjected to pulsatile pressure are investigated. The equations of motion are obtained based on the nonlinear Novozhilov shell theory via Lagrangian approach. The flow is set in motion by a pulsatile pressure gradient. The fluid is modeled as a Newtonian pulsatile flow and it is formulated using a hybrid model that contains the unsteady effects obtained from the linear potential flow theory and the pulsatile viscous effects obtained from the unsteady time-averaged Navier-Stokes equations. A numerical bifurcation analysis employs a refined reduced order model to investigate the dynamic behavior. The case of shells containing quiescent fluid subjected to the action of a pulsatile transmural pressure is also addressed. Geometrically nonlinear vibration response to pulsatile flow and transmural pressure are here presented via frequency-response curves and time histories. The vibrations involving both a driven mode and a companion mode, which appear due to the axial symmetry, are also investigated. This theoretical framework represents a pioneering study that could be of great interest for biomedical applications. In particular, in the future, a more refined model of the one here presented will possibly be applied to reproduce the dynamic behavior of vascular prostheses used for repairing and replacing damaged and diseased thoracic aorta in cases of aneurysm, dissection or coarctation. For this purpose, a pulsatile time-dependent blood flow model is here considered by applying physiological waveforms of velocity and pressure during the heart beating period. This study provides, for the first time in literature, a fully coupled fluid-structure interaction model with deep insights in the nonlinear vibrations of circular cylindrical shells subjected to pulsatile pressure and pulsatile flow.

  13. Mental distress and personality in women undergoing GnRH agonist versus GnRH antagonist protocols for assisted reproductive technology.

    Science.gov (United States)

    Stenbæk, D S; Toftager, M; Hjordt, L V; Jensen, P S; Holst, K K; Bryndorf, T; Holland, T; Bogstad, J; Pinborg, A; Hornnes, P; Frokjaer, V G

    2015-01-01

    Do mental distress and mood fluctuations in women undergoing GnRH agonist and GnRH antagonist protocols for assisted reproductive technology (ART) differ depending on protocol and the personality trait, neuroticism? ART treatment did not induce elevated levels of mental distress in either GnRH antagonist or agonist protocols but neuroticism was positively associated with increased mental distress, independent of protocols. ART treatment may increase mental distress by mechanisms linked to sex hormone fluctuations. General psychological characteristics, such as personality traits indexing negative emotionality, e.g. neuroticism, are likely to affect mental distress during ART treatment. A total of 83 women undergoing their first ART cycle were consecutively randomized 1:1 to GnRH antagonist (n = 42) or GnRH agonist (n = 41) protocol. The study population was a subgroup of a larger ongoing Danish clinical randomized trial and was established as an add-on in the period 2010-2012. Women in the GnRH antagonist protocol received daily injections with recombinant follicle-stimulating hormone, Puregon(®) and subcutaneous injections with GnRH antagonist, Orgalutran(®). Women in the GnRH agonist protocol received nasal administration of the GnRH agonist, Synarela(®) and subcutaneous injections with FSH, Puregon(®). The study design did not allow for a blinding procedure. All women self-reported the Profile of Mood States, the Perceived Stress Scale, the Symptom Checklist-92-Revised, and the Major Depression Inventory questionnaires, at baseline, at ART cycle day 35, on the day of oocyte pick-up, and on the day of hCG testing. Also, a series of Profile of Mood States were reported daily during pharmacological treatment to monitor mood fluctuations. The personality trait Neuroticism was assessed at baseline by the self-reported NEO-PI-R questionnaire. ART did not induce within- or between-protocol changes in any of the applied measures of mental distress. However, the GnRH

  14. ART Outcomes in GnRH Antagonist Protocol (Flexible) and Long GnRH Agonist Protocol during Early Follicular Phase in Patients with Polycystic Ovary Syndrome: A Randomized Clinical Trial

    Science.gov (United States)

    Mokhtar, Sara; Sadeghi, Mohammad Reza; Akhondi, Mohammad Mehdi; Zafardoust, Simin; Badenush, Bita; Fatemi, Farnaz; Nazari, Fattane; Kamali, Koorosh; Mohammadzade, Afsaneh

    2015-01-01

    Background: Since increased LH in the early follicular phase in PCOS patients especially in GnRH antagonist protocol could be associated with reduced oocyte quality and pregnancy and impared implantation. The current study was conducted to determine ART outcomes in GnRH antagonist protocol (flexible) and long GnRH agonist protocol and compare them with adding GnRH antagonist in GnRH antagonist (flexible) protocol during early follicular phase in patients with polycystic ovary syndrome undergoing ICSI. Methods: In this randomized clinical trial, 150 patients with polycystic ovary syndrome undergoing ICSI were enrolled from 2012 to 2014 and randomly assigned to receive either GnRH antagonist protocol during early and late follicular phase or GnRH antagonist protocol (flexible) or long GnRH agonist protocol. The clinical and laboratory pregnancy in three groups was determined and compared. In this context, the chi-square and Fisher's exact test and ANOVA were used for data analysis. Statistical significance was defined as p<0.05. Results: There was no statistically significant difference with respect to chemical pregnancy and clinical pregnancy between the three groups. Also, other indices such as number and quality of oocytes and embryos were alike. Conclusion: Totally, according to our results, GnRH antagonist protocol during early and late follicular phase and GnRH antagonist protocol (flexible) and long GnRH agonist protocol in patients with polycystic ovary syndrome undergoing ICSI are similarly effective and use of each one based on patients' condition and physicians' opinion could be considered. PMID:26913233

  15. Morinda Officinalis Polysaccharides Stimulate Hypothalamic GnRH Secretion in Varicocele Progression

    Directory of Open Access Journals (Sweden)

    Zhu Zhu

    2017-01-01

    Full Text Available Varicoceles (VCs are the predominant cause of male infertility and are a risk factor for chronic venous disease. Morinda officinalis (M. officinalis is a traditional Chinese medicine used to tonify the kidney and strengthen yang. In this study, we evaluated the effects of water-soluble polysaccharides extracted from M. officinalis (MOPs on gonadotropin-release hormone (GnRH secretion in a classic experimental left VC (ELV rat model. Intragastric administration of MOPs at a dose ranging from 50 mg kg−1 to 100 mg kg−1 facilitated improvements in sperm parameters and seminiferous epithelial structures, modulated serum hormone profiles, and stimulated GnRH synthesis and release in the hypothalamus. MOPs also promoted spinogenesis and functional spine maturation in the arcuate nuclei (Arc, wherein they acted mainly on Kiss1 and GnRH neurons. Moreover, MOP-mediated Kisspeptin-GPR54 pathway upregulation and MAPK phosphorylation activation may have been responsible for increases in GnRH synthesis and release. Collectively, the findings of this study indicate that MOPs were effective in stimulating GnRH secretion, possibly by upregulating the Kiss1/GPR54 pathway and enhancing synaptic plasticity, and that MOPs can serve as a therapy for early VCs.

  16. Evolution of vertebrate GnRH receptors from the perspective of a basal vertebrate

    Directory of Open Access Journals (Sweden)

    Stacia A Sower

    2012-11-01

    Full Text Available This minireview provides the current status on gonadotropin-releasing hormone receptors (GnRH-R in vertebrates, from the perspective of a basal vertebrate, the sea lamprey, and provides an evolutionary scheme based on the recent advance of whole genome sequencing. In addition, we provide a perspective on the functional divergence and evolution of the receptors. In this review we use the phylogenetic classification of vertebrate GnRH receptors that groups them into three clusters: type I (mammalian and non-mammalian, type II, and type III GnRH receptors. New findings show that the sea lamprey has two type III-like GnRH receptors and an ancestral type GnRH receptor that is more closely related to the type II-like receptors. These two novel GnRH receptors along with lGnRH-R-1 share similar structural features and amino acid motifs common to other known gnathostome type II/III receptors. Recent data analyses of the lamprey genome provide strong evidence that 2 whole rounds of genome duplication (2R occurred prior to the gnathostome-agnathan split. Based on our current knowledge, it is proposed that lGnRH-R-1 evolved from an ancestor of the type II receptor following a vertebrate-shared genome duplication and that the two type III receptors resulted from a duplication within lamprey of a gene derived from a lineage shared by many vertebrates.

  17. Combined ovulation triggering with GnRH agonist and hCG in IVF patients.

    Science.gov (United States)

    Kasum, Miro; Kurdija, Kristijan; Orešković, Slavko; Čehić, Ermin; Pavičić-Baldani, Dinka; Škrgatić, Lana

    2016-11-01

    The aim of the review is to analyse the combination of a gonadotrophin releasing hormone (GnRH) agonist with a human chorionic gonadotrophin (hCG) trigger, for final oocyte maturation in in vitro fertilisation (IVF) cycles. The concept being a ''dual trigger'' combines a single dose of the GnRH agonist with a reduced or standard dosage of hCG at the time of triggering. The use of a GnRH agonist with a reduced dose of hCG in high responders demonstrated luteal phase support with improved pregnancy rates, similar to those after conventional hCG and a low risk of ovarian hyperstimulation syndrome (OHSS). The administration of a GnRH agonist and a standard hCG in normal responders, demonstrated significantly improved live-birth rates and a higher number of embryos of excellent quality, or cryopreserved embryos. The concept of the ''double trigger" represents a combination of a GnRH agonist and a standard hCG, when used 40 and 34 h prior to ovum pick-up, respectively. The use of the ''double trigger" has been successfully offered in the treatment of empty follicle syndrome and in patients with a history of immature oocytes retrieved or with low/poor oocytes yield. Further prospective studies are required to confirm the aforementioned observations prior to clinical implementation.

  18. Electrically actuatable smart nanoporous membrane for pulsatile drug release.

    Science.gov (United States)

    Jeon, Gumhye; Yang, Seung Yun; Byun, Jinseok; Kim, Jin Kon

    2011-03-09

    We report on the fabrication of electrically responsive nanoporous membrane based on polypyrrole doped with dodecylbenzenesulfonate anion (PPy/DBS) that was electropolymerized on the upper part of anodized aluminum oxide membrane. The membrane has regular pore size and very high pore density. Utilizing a large volume change of PPy/DBS depending on electrochemical state, the pore size was acutated electrically. The actuation of the pores was experimentally confirmed by in situ atomic force microscopy and in situ flux measurement. We also demonstrated successfully pulsatile (or on-demand) drug release by using fluorescently labeled protein as a model drug. Because of a fast switching time (less than 10 s) and high flux of the drugs, this membrane could be used for emergency therapy of angina pectoris and migraine, which requires acute and on-demand drug delivery, and hormone-related disease and metabolic syndrome.

  19. Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist

    DEFF Research Database (Denmark)

    Humaidan, P; Bungum, L; Bungum, M

    2006-01-01

    Previous studies found a poor clinical outcome when a GnRH agonist (GnRHa) was used to trigger ovulation in GnRH antagonist IVF/ICSI cycles. This study aimed to determine the clinical and endocrine effects as well the optimal timing of HCG supplementation. Forty-five normogonadotrophic IVF/ICSI p...

  20. Class-C SOX Transcription Factors Control GnRH Gene Expression via the Intronic Transcriptional Enhancer

    Science.gov (United States)

    Kim, Hee-Dae; Choe, Han Kyoung; Chung, Sooyoung; Kim, Myungjin; Seong, Jae Young

    2011-01-01

    GnRH is a pivotal hypothalamic neurohormone governing reproduction and sexual development. Because transcriptional regulation is crucial for the spatial and temporal expression of the GnRH gene, a region approximately 3.0 kb upstream of the mammalian GnRH promoter has been extensive studied. In the present study, we demonstrate a transcription-enhancer located in the first intron (intron A) region of the GnRH gene. This transcriptional enhancer harbors putative sex-determining region Y-related high-mobility-group box (SOX) family transcription factor-binding sites, which are well conserved across many mammalian species. The class-C SOX member proteins (SOX-C) (SOX4 and SOX11) specifically augment this transcriptional activation by binding to these SOX-binding sites. In accordance, SOX11 is highly enriched in immortalized GnRH-producing GT1-1 cells, and suppression of its expression significantly decreases GnRH gene expression as well as GnRH secretion. Chromatin immunoprecipitation shows that endogenous SOX-C factors recognize and bind to the intronic enhancer in GT1-1 cells and the hypothalamus. Accompanying immunohistochemical analysis demonstrates that SOX4 or SOX11 are highly expressed in the majority of hypothalamic GnRH neurons in adult mice. Taken together, these findings demonstrate that SOX-C transcription factors function as important transcriptional regulators of cell type-specific GnRH gene expression by acting on the intronic transcriptional enhancer. PMID:21527504

  1. Long-term effects of GnRH agonists on fertility and behaviour.

    Science.gov (United States)

    Goericke-Pesch, S

    2017-04-01

    This review aimed to summarize the present knowledge about the effects of GnRH agonist slow-release implants (GnRH A-SRI) on fertility and behaviour in male and female dogs and cats with special focus on deslorelin. Following an initial stimulation of gonadotropin and testosterone secretion possibly associated with an improved semen quality, GnRH A-SRI induce long-term depression of fertility in male dogs and cats with, however, a large individual variation in onset and duration of efficacy especially in cats. The GnRH A-SRI furthermore interfere with testosterone-dependent/affected behaviour; a significant positive effect in reducing sexual behaviour and libido, hypersexuality, intermale dominance and excessive territorial urine marking has been described. Rates of improvement of the respective behaviour are comparable to those after surgical castration, making GnRH A-SRI a valuable option to predict castration-related effects on behaviour and to identify animals where surgical castration will not be beneficial. No effect has been seen in reducing aggression towards humans indicating the need for behavioural therapy to control this problem. Effects on spermatogenesis, steroidogenesis and behaviour have by now been shown to be fully reversible. Knowledge in females is more limited, and particularly, the initial induction of a possibly fertile oestrus and individual variation in duration of efficacy remain problems in bitches and queens treated for suppression of fertility. However, long-term suppression of oestrous cycle and fertility seems to be possible with induced effects shown to be reversible including restoration of normal fertility after the end of efficacy/GNRH A-SRI removal. © 2016 Blackwell Verlag GmbH.

  2. The effects of a slow release GnRH agonist implant on male rabbits

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin; Groeger, Gesa; Wehrend, Axel

    2015-01-01

    . Long-term application of a GnRH agonist implant results in a fully reversible "hormonal" castration in male dogs, cats, boars and many other species. Therefore, the present study using New Zealand White hybrid and German Giant rabbits aimed to investigate the effects of a 4.7mg deslorelin implant...... in SG and not different from CG. Application of a slow release GnRH agonist implant does not induce hormonal castration in male rabbits over a period of 90 days indicating that it is not a suitable alternative to surgical castration in this species....

  3. Glial-gonadotrophin hormone (GnRH) neurone interactions in the median eminence and the control of GnRH secretion.

    Science.gov (United States)

    Ojeda, S R; Lomniczi, A; Sandau, U S

    2008-06-01

    A wealth of information now exists showing that glial cells are actively involved in the cell-cell communication process generating and disseminating information within the central nervous system. In the hypothalamus, two types of glial cells, astrocytes and ependymal cells lining the latero-ventral portion of the third ventricle (known as tanycytes), regulate the secretory activity of neuroendocrine neurones. This function, initially described for astrocytes apposing magnocellular neurones, has been more recently characterised for neurones secreting gonadotrophin hormone-releasing hormone (GnRH). The available evidence suggests that glial cells of the median eminence regulate GnRH secretion via two related mechanisms. One involves the production of growth factors acting via receptors with tyrosine kinase activity. The other involves plastic rearrangements of glia-GnRH neurone adhesiveness. GnRH axons reach the median eminence, at least in part, directed by basic fibroblast growth factor. Their secretory activity is facilitated by insulin-like growth factor 1 and members of the epidermal growth factor family. A structural complement to these soluble molecules is provided by at least three cell-cell adhesion systems endowed with signalling capabilities. One of them uses the neuronal cell adhesion molecule (NCAM), another employs the synaptic cell adhesion molecule (SynCAM), and the third one consists of neuronal contactin interacting with glial receptor-like protein tyrosine phosphatase-beta. It is envisioned that, within the median eminence, soluble factors and adhesion molecules work coordinately to control delivery of GnRH to the portal vasculature.

  4. Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review.

    Science.gov (United States)

    Pandit, Vinay; Kumar, Ajay; Ashawat, Mahendra S; Verma, Chander P; Kumar, Pravin

    2017-01-01

    Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Role of color Doppler US in the evaluation of uterine leiomyoma treated with gonadotrophin-releasing hormone (GnRH) agonist (Zoladex)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Sik; Sohn, Cheol Ho; Lee, Tae Sung [Keimyung University Dongsan Medical Center, Taegu (Korea, Republic of)

    1999-03-15

    To access the role of color Doppler US in the evaluation of uterine leiomyoma treated with GnRH agonist (Zoladex). Out of 25 patients with uterine leiomyoma treated with Zoladex, nineteen cases of leiomyoma in 18 women who had US examination before and after medication were included in this study. Zoladex was injected subcutaneously three times within three months. Both gray scale and color Doppler US were obtained before and 1-3 months after the medication. The size, volume, location and internal echoes of the leiomyoma were recorded with gray scale US. Changes in the amount of color signal within leiomyomas were recorded. Pulsatility index (PI), resistive index (RI), peak systolic velocity (PSV) of both uterine artery and arteries within leiomyomas were also recorded. The image findings of good response group and poor response group in which the volume reduction of the leiomyoma was above or below 50% respectively were compared with each other. The reduction of the volume of leiomyoma was compared between a group with decrease in the amount of color signals during follow-up US and a group with increase or no change. Mean reduction of the volume of leiomyomas was 52%. Changes in the amount of color signals of the leiomyoma, PI, RI, PSV obtained from the arteries within leiomyomas were not correlated with the change of the volume of leiomyomas. PSV of uterine artery in one month follow-up and PI of two month follow-up were correlated with the changes of the volume of leiomyomas (p<0.05). RI of uterine artery in two month follow-up was useful in prediction of the good response group and the poor response group (p<0.05). The prediction of the volume reduction of leiomyoma following Zoladex medication might be possible by obtaining RI of uterine artery in two month follow-up. Doppler US of the arteries within the leiomyoma was not useful.

  6. Cerebral blood flow and intracranial pulsatility studied with MRI: measurement, physiological and pathophysiological aspects

    Energy Technology Data Exchange (ETDEWEB)

    Waahlin, Anders

    2012-07-01

    During each cardiac cycle pulsatile arterial blood inflates the vascular bed of the brain, forcing cerebrospinal fluid (CSF) and venous blood out of the cranium. Excessive arterial pulsatility may be part of a harmful mechanism causing cognitive decline among elderly. Additionally, restricted venous flow from the brain is suggested as the cause of multiple sclerosis. Addressing hypotheses derived from these observations requires accurate and reliable investigational methods. This work focused on assessing the pulsatile waveform of cerebral arterial, venous and CSF flows. The overall aim of this dissertation was to explore cerebral blood flow and intracranial pulsatility using MRI, with respect to measurement, physiological and pathophysiological aspects.Two-dimensional phase contrast magnetic resonance imaging (2D PCMRI) was used to assess the pulsatile waveforms of cerebral arterial, venous and CSF flow. The repeatability was assessed in healthy young subjects. The 2D PCMRI measurements of cerebral arterial, venous and CSF pulsatility were generally repeatable but the pulsatility decreased systematically during the investigation. A method combining 2D PCMRI measurements with invasive CSF infusion tests to determine the magnitude and distribution of compliance within the craniospinal system was developed and applied in a group of healthy elderly. The intracranial space contained approximately two thirds of the total craniospinal compliance. The magnitude of craniospinal compliance was less than suggested in previous studies. The vascular hypothesis for multiple sclerosis was tested. Venous drainage in the internal jugular veins was compared between healthy controls and multiple sclerosis patients using 2D PCMRI. For both groups, a great variability in the internal jugular flow was observed but no pattern specific to multiple sclerosis could be found. Relationships between regional brain volumes and potential biomarkers of intracranial cardiac-related pulsatile

  7. Functional Significance of GnRH and Kisspeptin, and Their Cognate Receptors in Teleost Reproduction

    Directory of Open Access Journals (Sweden)

    RENJITHA eGOPURAPPILLY

    2013-03-01

    Full Text Available Guanine nucleotide binding protein (G-protein-coupled receptors (GPCRs are eukaryotic transmembrane proteins found in all living organisms. Their versatility and roles in several physiological processes make them the single largest family of drug targets. Comparative genomic studies using various model organisms have provided useful information about target receptors. The similarity of the genetic makeup of teleosts to that of humans and other vertebrates aligns with the study of GPCRs. Gonadotropin-releasing hormone (GnRH represents a critical step in the reproductive process through its cognate GnRH receptors (GnRHRs. Kisspeptin (Kiss1 and its cognate GPCR, GPR54 (=kisspeptin receptor, Kiss-R, have recently been identified as a critical signalling system in the control of reproduction. The Kiss1/GPR54 system regulates GnRH release, which is vital to pubertal development and vertebrate reproduction. This review highlights the physiological role of kisspeptin-Kiss-R signalling in the reproductive neuroendocrine axis in teleosts through the modulation of GnRH release. Moreover, we also review the recent developments in GnRHR and Kiss-R with respect to their structural variants, signalling mechanisms, ligand interactions and functional significance. Finally, we discuss the recent progress in identifying many teleost GnRH-GnRHR and kisspeptin-Kiss-R systems and will consider their physiological significance in the control of reproduction.

  8. Effect of gonadotropin-releasing hormone (GnRH) treatment on ...

    African Journals Online (AJOL)

    Administrator

    2011-09-28

    Sep 28, 2011 ... 1169-1171. Eppleston J, Roberts EM (1991). Effect of time of PMSG and GnRH on the time of ovulation, LH secretion and reproductive performance after intrauterine insemination with frozen ram semen. Anim. Reprod. Sci. 26: 227-237. Evans NP, Dahl GE, Caraty A, Padmanabhan V, Thrun LA, Karsch FJ.

  9. Social Crowding during Development Causes Changes in GnRH1 DNA Methylation.

    Science.gov (United States)

    Alvarado, Sebastian G; Lenkov, Kapa; Williams, Blake; Fernald, Russell D

    2015-01-01

    Gestational and developmental cues have important consequences for long-term health, behavior and adaptation to the environment. In addition, social stressors cause plastic molecular changes in the brain that underlie unique behavioral phenotypes that also modulate fitness. In the adult African cichlid, Astatotilapia burtoni, growth and social status of males are both directly regulated by social interactions in a dynamic social environment, which causes a suite of plastic changes in circuits, cells and gene transcription in the brain. We hypothesized that a possible mechanism underlying some molecular changes might be DNA methylation, a reversible modification made to cytosine nucleotides that is known to regulate gene function. Here we asked whether changes in DNA methylation of the GnRH1 gene, the central regulator of the reproductive axis, were altered during development of A. burtoni. We measured changes in methylation state of the GnRH1 gene during normal development and following the gestational and developmental stress of social crowding. We found differential DNA methylation within developing juveniles between 14-, 28- and 42-day-old. Following gestational crowding of mouth brooding mothers, we saw differential methylation and transcription of GnRH1 in their offspring. Taken together, our data provides evidence for social control of GnRH1 developmental responses to gestational cues through DNA methylation.

  10. Is the use of a GnRH antagonist effective in patients with polycystic ...

    African Journals Online (AJOL)

    offered controlled ovarian stimulation (COS) and in vitro fertilisation (IVF) technology. Aim. The aim of this study was to assess whether there was a difference in the pregnancy outcomes of women with PCOS when a standard gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix) protocol was used for ovarian ...

  11. Receptor-mediated binding and uptake of GnRH agonist and antagonist by pituitary cells

    Energy Technology Data Exchange (ETDEWEB)

    Jennes, L.; Stumpf, W.E.; Conn, P.M.

    1984-01-01

    The intracellular pathway of an enzyme resistant GnRH agonist (D- Lys6 -GnRH) conjugated to ferritin or to colloidal gold was followed in cultured pituitary cells. After an initial uniform distribution over the cell surface of gonadotropes, the electrondense marker was internalized, either individually or in small groups. After longer incubation times, the marker appeared in the lysosomal compartment and the Golgi apparatus, where it could be found in the vesicular as well as cisternal portion. In addition, the receptor-mediated endocytosis of the GnRH antagonist D-p-Glu1-D-Phe2-D-Trp3-D- Lys6 -GnRH was studied by light and electron microscopic autoradiography after 30 and 60 min of incubation to ensure uptake. At both time points, in in vitro as well as in vivo studies, silver grains were localized over cytoplasmic organelles of castration cells, including dilated endoplasmic reticulum, lysosomes, and clear vesicles. No consistent association with cell nuclei, mitochondria, or secretory vesicles could be observed. The results suggest that both agonist and antagonist are binding selectively to the plasma membrane of gonadotropes and subsequently are taken up via receptor-mediated endocytosis for degradation or possible action on synthetic processes.

  12. Superovulatory response in Boer goats pre-treated with a GnRH ...

    African Journals Online (AJOL)

    The aim of this study was to evaluate the ovarian response and embryo recovery rates in Boer goat does superovulated with pFSH following a pre-treatment with a GnRH agonist (GnRHa) outside the natural breeding season. Oestrus was synchronised in 22 does with CIDR\\'s for 17 days, and these were superovulated with ...

  13. Hormonal responses to GnRH injection given at different stages of ...

    African Journals Online (AJOL)

    The objective of the present study was to evaluate the hormonal responses of buffaloes to GnRH injections given at different moments of the estrous cycle. The estrous cycles of 15 buffaloes were synchronized with 2 im injections of prostaglandin F2α given 11 days apart. The buffalos were randomly assigned to 1 of 3 ...

  14. Effect of gonadotropin-releasing hormone (GnRH) treatment on ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the effects of gonadotropin-releasing hormone (GnRH) administration on the induction of multiple births in synchronized Afshari ewes. 16 cycling, multiparous fat-tailed Iranian Afshari ewes, weighing 66.5 ± 2.5 kg, were used in the trail. Estrus was synchronized using controlled ...

  15. Regulation of GnRH receptors by progesterone and inhibin in ovine pituitary cell culture

    Energy Technology Data Exchange (ETDEWEB)

    Laws, S.C.

    1988-01-01

    The effects of progesterone (P{sub 4}) and the gonadal protein, inhibin, on gonadotropin-releasing hormone (GnRH) receptor number and binding affinity were investigated in vitro, using ovine pituitary cells in culture. Changes in GnRH binding were correlated with GnRH-stimulated luteinizing hormone (LH) release following pretreatment with P{sub 4} and inhibin. Ovine pituitary cells in culture were preincubated with P{sub 4} or porcine inhibin (I{sub P}) for 24 or 48 hours (h). Cells were collected and analyzed for GnRH binding using a radioligand-receptor assay. des-Gly{sup 10}-(D-Ala{sup 6})-LHRH-ethyl-amide was used as the radiolabeled GnRh superagonist analog (mono-{sup 125}I-GnRH-A) and as competing ligand. Treatment with P{sub 4} progressively decreased GnRH-A binding capacity by 44.3% and 71.8% of the control following pretreatment for 24 or 48 h, respectively. When P{sub 4} was removed from the cultures, GnRH-A binding capacity partially returned to control levels within 24 h. Decreased GnRH-A binding was closely correlated with the reduction in GnRH-stimulated LH release which was observed following 24 or 48 h pretreatment with P{sub 4}.

  16. EFFECT TN EWES OF OESTROGEN PRIMING AND GnRH ON LH ...

    African Journals Online (AJOL)

    EFFECT TN EWES OF OESTROGEN PRIMING AND GnRH ON LH RELEASE. AND LUTEAL FUNCTION DURING EARLY LACTATION IN SPRING. Receipt of MS 22-03-1979. C.D. Hamilton*, A.W. Lishman and P.A. Lamb. Department ol Animal Science, Universitlt ol'Natol, nercrmaitzburg, 3200. (Key words. Oestrogen ...

  17. Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release.

    Science.gov (United States)

    Ansel, L; Bentsen, A H; Ancel, C; Bolborea, M; Klosen, P; Mikkelsen, J D; Simonneaux, V

    2011-09-01

    In seasonal breeders, reproduction is synchronised by day length via the pineal hormone melatonin. In short winter days (short day, SD), the Syrian hamster displays a complete gonadal atrophy together with a marked reduction in expression of kisspeptins (Kp), a family of potent hypothalamic stimulators of GNRH neurons. Both central and peripheral acute injections of Kp have been reported to activate the gonadotropic axis in mammals. The aim of this study was to determine if and how peripheral administration of Kp54 could restore gonadal function in photo-inhibited hamsters. Testicular activity of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong increase in circulating testosterone. The activation of pituitary cells by Kp was inhibited by preadministration of the GNRH receptor antagonist acyline. Altogether, our results demonstrate that peripheral Kp54 activates the gonadotropic axis by stimulating GNRH release and indicate that an appropriate protocol of long-term systemic Kp administration can recrudesce a photo-inhibited reproductive axis.

  18. Functional Significance of GnRH and Kisspeptin, and Their Cognate Receptors in Teleost Reproduction

    Science.gov (United States)

    Gopurappilly, Renjitha; Ogawa, Satoshi; Parhar, Ishwar S.

    2012-01-01

    Guanine nucleotide binding protein (G-protein)-coupled receptors (GPCRs) are eukaryotic transmembrane proteins found in all living organisms. Their versatility and roles in several physiological processes make them the single largest family of drug targets. Comparative genomic studies using various model organisms have provided useful information about target receptors. The similarity of the genetic makeup of teleosts to that of humans and other vertebrates aligns with the study of GPCRs. Gonadotropin-releasing hormone (GnRH) represents a critical step in the reproductive process through its cognate GnRH receptors (GnRHRs). Kisspeptin (Kiss1) and its cognate GPCR, GPR54 (=kisspeptin receptor, Kiss-R), have recently been identified as a critical signaling system in the control of reproduction. The Kiss1/Kiss-R system regulates GnRH release, which is vital to pubertal development and vertebrate reproduction. This review highlights the physiological role of kisspeptin-Kiss-R signaling in the reproductive neuroendocrine axis in teleosts through the modulation of GnRH release. Moreover, we also review the recent developments in GnRHR and Kiss-R with respect to their structural variants, signaling mechanisms, ligand interactions, and functional significance. Finally, we discuss the recent progress in identifying many teleost GnRH-GnRHR and kisspeptin-Kiss-R systems and consider their physiological significance in the control of reproduction. PMID:23482509

  19. Multiphase hemodynamic simulation of pulsatile flow in a coronary artery.

    Science.gov (United States)

    Jung, Jonghwun; Lyczkowski, Robert W; Panchal, Chandrakant B; Hassanein, Ahmed

    2006-01-01

    A multiphase transient non-Newtonian three-dimensional (3-D) computational fluid dynamics (CFD) simulation has been performed for pulsatile hemodynamics in an idealized curved section of a human coronary artery. We present the first prediction, to the authors' knowledge, of particulate buildup on the inside curvature using the multiphase theory of dense suspension hemodynamics. In this study, the particulates are red blood cells (RBCs). The location of RBC buildup on the inside curvature correlates with lower wall shear stress (WSS) relative to the outside curvature. These predictions provide insight into how blood-borne particulates interact with artery walls and hence, have relevance for understanding atherogenesis since clinical observations show that atherosclerotic plaques generally form on the inside curvatures of arteries. The buildup of RBCs on the inside curvature is driven by the secondary flow and higher residence times. The higher viscosity in the central portion of the curved vessel tends to block their flow, causing them to migrate preferentially through the boundary layer. The reason for this is the nearly neutrally buoyant nature of the dense two-phase hemodynamic flow. The two-phase non-Newtonian viscosity model predicts greater shear thinning than the single-phase non-Newtonian model. Consequently, the secondary flow induced in the curvature is weaker. The waveforms for computed hemodynamic parameters, such as hematocrit, WSS, and viscosity, follow the prescribed inlet velocity waveforms. The lower oscillatory WSS produced on the inside curvature has implications for understanding thickening of the intimal layer.

  20. Pulsatile Versus Oscillatory Shear Stress Regulates NADPH Oxidase Subunit Expression

    Science.gov (United States)

    Hwang, Juliana; Ing, Michael H.; Salazar, Adler; Lassègue, Bernard; Griendling, Kathy; Navab, Mohamad; Sevanian, Alex; Hsiai, Tzung K.

    2015-01-01

    Shear stress regulates endothelial nitric oxide and superoxide (O2−·) production, implicating the role of NADPH oxidase activity. It is unknown whether shear stress regulates the sources of reactive species production, consequent low-density lipoprotein (LDL) modification, and initiation of inflammatory events. Bovine aortic endothelial cells (BAECs) in the presence of 50 μg/mL of native LDL were exposed to (1) pulsatile flow with a mean shear stress (τave) of 25 dyne/cm2 and (2) oscillating flow at τave of 0. After 4 hours, aliquots of culture medium were collected for high-performance liquid chromatography analyses of electronegative LDL species, described as LDL− and LDL2−. In response to oscillatory shear stress, gp91phox mRNA expression was upregulated by 2.9±0.3-fold, and its homologue, Nox4, by 3.9±0.9-fold (PBAEC binding (PBAEC binding. The flow-dependent LDL oxidation is determined in part by the NADPH oxidase activity. The formation of modified LDL via O2−· production may also affect the regulation of monocyte chemoattractant protein-1 expression and monocyte/BAEC binding. PMID:14593003

  1. Numerical washout study of a pulsatile total artificial heart.

    Science.gov (United States)

    Sonntag, Simon J; Kaufmann, Tim A S; Büsen, Martin R; Laumen, Marco; Gräf, Felix; Linde, Torsten; Steinseifer, Ulrich

    2014-03-01

    For blood pumps with long term indication, blood stagnation can result in excessive thromboembolic risks for patients. This study numerically investigates the washout performance of the left pump chamber of a pulsatile total artificial heart (TAH) as well as the sensitivity of the rotational orientation of the inlet bileaflet mechanical heart valve (MHV) on blood stagnation. To quantitatively evaluate the washout efficiency, a fluid-structure interaction (FSI) simulation of the artificial heart pumping process was combined with a blood washout model. Four geometries with different orientations (0°, 45°, 90° and 135°) of the inlet valve were compared with respect to washout performance. The calculated flow field showed a high level of agreement with particle image velocimetry (PIV) measurements. Almost complete washout was achievable after three ejection phases. Remains of old blood in relation to the chamber volume was below 0.6% for all configurations and were mainly detected opposite to the inlet and outlet port at the square edge where the membrane and the pump chamber are connected. Only a small variation in the washout efficiency and the general flow field was observed. An orientation of 0° showed minor advantages with respect to blood stagnation and recirculation. Bileaflet MHVs were demonstrated to be only slightly sensitive to rotation regarding the washout performance of the TAH. The proposed numerical washout model proved to be an adequate tool to quantitatively compare different configurations and designs of the artificial organ regarding the potential for blood stagnation where experimental measurements are limited.

  2. Pulsatile cerebrospinal fluid dynamics in the human brain.

    Science.gov (United States)

    Linninger, Andreas A; Tsakiris, Cristian; Zhu, David C; Xenos, Michalis; Roycewicz, Peter; Danziger, Zachary; Penn, Richard

    2005-04-01

    Disturbances of the cerebrospinal fluid (CSF) flow in the brain can lead to hydrocephalus, a condition affecting thousands of people annually in the US. Considerable controversy exists about fluid and pressure dynamics, and about how the brain responds to changes in flow patterns and compression in hydrocephalus. This paper presents a new model based on the first principles of fluid mechanics. This model of fluid-structure interactions predicts flows and pressures throughout the brain's ventricular pathways consistent with both animal intracranial pressure (ICP) measurements and human CINE phase-contrast magnetic resonance imaging data. The computations provide approximations of the tissue deformations of the brain parenchyma. The model also quantifies the pulsatile CSF motion including flow reversal in the aqueduct as well as the changes in ICPs due to brain tissue compression. It does not require the existence of large transmural pressure differences as the force for ventricular expansion. Finally, the new model gives an explanation of communicating hydrocephalus and the phenomenon of asymmetric hydrocephalus.

  3. Developed pulsatile flow in a deployed coronary stent.

    Science.gov (United States)

    Banerjee, Rupak K; Devarakonda, Surendra B; Rajamohan, Divakar; Back, Lloyd H

    2007-01-01

    The patho-physiologic process of restenosis and tissue growth may not be completely eliminated and is the primary concern of clinicians performing angioplasty and stent implantation procedures. Recent evidence suggests that the restenosis process is influenced by several factors: (1) geometry and size of vessel; (2) stent design; and (3) it's location that alter hemodynamic parameters, including local wall shear stress (WSS) distributions. The present three-dimensional (3D) analysis of pulsatile flow in a deployed coronary stent: (1) shows complex 3D variation of hemodynamic parameters; and (2) quantifies the changes in local WSS distributions for developed flow and compares with recently published WSS data for developing flow. Higher order of magnitude of WSS of 290 dyn/cm(2) is observed on the surface of cross-link intersections at the entrance of the stent for developed flow, which is about half of that for developing flow. Low WSS of 0.8 dyn/cm(2) and negative WSS of -8 dyn/cm(2) are seen at the immediate upstream and downstream regions of strut intersections. Persistent recirculation is observed at the downstream region of each strut cross-link and the regions of low and negative WSS may lead to patho-physiologic conditions near the stented region. The key finding of this study is that the location of stent in the coronary artery determines the developing or developed nature of the flow, which in turn, results in varied level of WSS.

  4. PLATELET ADHESION TO POLYURETHANE UREA UNDER PULSATILE FLOW CONDITIONS

    Science.gov (United States)

    Navitsky, Michael A.; Taylor, Joshua O.; Smith, Alexander B.; Slattery, Margaret J.; Deutsch, Steven; Siedlecki, Christopher A.; Manning, Keefe B.

    2014-01-01

    Platelet adhesion to a polyurethane urea surface is a precursor to thrombus formation within blood-contacting cardiovascular devices, and platelets have been found to adhere strongly to polyurethane surfaces below a shear rate of approximately 500 s−1. The aim of the current work is to determine platelet adhesion properties to the polyurethane urea surface as a function of time varying shear exposure. A rotating disk system is used to study the influence of steady and pulsatile flow conditions (e.g. cardiac inflow and sawtooth waveforms) for platelet adhesion to the biomaterial surface. All experiments retain the same root mean square angular rotation velocity (29.63 rad/s) and waveform period. The disk is rotated in platelet rich bovine plasma for two hours with adhesion quantified by confocal microscopy measurements of immunofluorescently labeled bovine platelets. Platelet adhesion under pulsating flow is found to exponentially decay with increasing shear rate. Adhesion levels are found to depend upon peak platelet flux and shear rate regardless of rotational waveform. In combination with flow measurements, these results may be useful for predicting regions susceptible to thrombus formation within ventricular assist devices. PMID:24721222

  5. Modelling retinal pulsatile blood flow from video data.

    Science.gov (United States)

    Betz-Stablein, Brigid; Hazelton, Martin L; Morgan, William H

    2016-09-01

    Modern day datasets continue to increase in both size and diversity. One example of such 'big data' is video data. Within the medical arena, more disciplines are using video as a diagnostic tool. Given the large amount of data stored within a video image, it is one of most time consuming types of data to process and analyse. Therefore, it is desirable to have automated techniques to extract, process and analyse data from video images. While many methods have been developed for extracting and processing video data, statistical modelling to analyse the outputted data has rarely been employed. We develop a method to take a video sequence of periodic nature, extract the RGB data and model the changes occurring across the contiguous images. We employ harmonic regression to model periodicity with autoregressive terms accounting for the error process associated with the time series nature of the data. A linear spline is included to account for movement between frames. We apply this model to video sequences of retinal vessel pulsation, which is the pulsatile component of blood flow. Slope and amplitude are calculated for the curves generated from the application of the harmonic model, providing clinical insight into the location of obstruction within the retinal vessels. The method can be applied to individual vessels, or to smaller segments such as 2 × 2 pixels which can then be interpreted easily as a heat map. © The Author(s) 2016.

  6. CT evaluation of sigmoid plate dehiscence causing pulsatile tinnitus

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Pengfei; Lv, Han; Dong, Cheng; Wang, Zhenchang [Capital Medical University, Department of Radiology, Beijing Friendship Hospital, Beijing (China); Niu, Yantao; Xian, Junfang [Capital Medical University, Department of Radiology, Beijing Tongren Hospital, Beijing (China)

    2016-01-15

    To evaluate the characteristics of sigmoid plate dehiscence (SPD) causing pulsatile tinnitus (PT) on CT arteriography and venography (CTA + V). Thirty PT patients treated successfully with SPD reconstruction were enrolled. Sixty asymptomatic patients were matched. The location, extent, number of SPD cases and concomitant signs, including venous outflow dominance, transverse sinus stenosis, high jugular bulb, temporal bone pneumatization, height of pituitary gland and pituitary fossa, abnormal mastoid emissary vein, were detected and compared using CTA + V. More than one SPD was found on the symptomatic side in 13/30 PT patients (43.3 %). The upper segment of the sigmoid plate was involved in 29/44 SPDs in the vertical direction (65.9 %); the lateral wall was involved in 38/44 SPDs in the horizontal direction (86.4 %). Singular SPD was detected in 3/60 asymptomatic patients (1.67 ± 0.35 mm{sup 2}), less so in PT patients (7.97 ± 5.17 mm{sup 2}). Compared with the control group, ipsilateral venous outflow dominance, high jugular bulb and bilateral transverse sinus stenosis were more common in the PT group, together with deeper pituitary fossa and flatter pituitary glands. SPD causing PT has characteristic CT findings. It may be generated by vascular or intracranial pressure abnormalities and act as a common key to triggering PT's perception. (orig.)

  7. Chronic Pulsatile Hyperglycemia Reduces Insulin Secretion and Increases Accumulation of Reactive Oxygen Species in Fetal Sheep Islets

    Science.gov (United States)

    Green, Alice S.; Chen, Xiaochuan; Macko, Antoni R.; Anderson, Miranda J.; Kelly, Amy C.; Hart, Nathaniel J.; Lynch, Ronald M.; Limesand, Sean W.

    2012-01-01

    Children from diabetic pregnancies have a greater incidence of Type 2 diabetes. Our objective was to determine if exposure to mild-moderate hyperglycemia, modeling managed diabetic pregnancies, affects fetal β-cell function. In sheep fetuses β-cell responsiveness was examined after two weeks of sustained hyperglycemia with 3 pulses/day, mimicking postprandial excursions, and compared to saline-infused controls (n=10). Two pulsatile hyperglycemia treatments were studied: mild (mPHG, n=5) with +15% sustained and +55% pulse; and moderate (PHG, n=10) with +20% sustained and +100% pulse. Fetal glucose-stimulated insulin secretion and glucose potentiated arginine insulin secretion were lower (Pinsulin) but not mPHG fetuses (1.21±0.08 and 4.25±0.56 ng/ml) compared to controls (1.58±0.25 and 4.51±0.56 ng/ml). Islet insulin content was 35% lower in PHG and 35% higher in mPHG versus controls (PInsulin secretion and maximally stimulated insulin release were also reduced (Pinsulin content. Isolated PHG islets also had 63% greater (Pinsulin resistance. Our findings show that PHG induced dysregulation of islet ROS handling and decreased islet insulin content, but these outcomes are independent. The β-cell outcomes were dependent on the severity of hyperglycemia because mPHG fetuses had no distinguishable impairments in ROS handling or insulin secretion but greater insulin content. PMID:22182602

  8. Ectopic pregnancy risk factors for ART patients undergoing the GnRH antagonist protocol: a retrospective study.

    Science.gov (United States)

    Weiss, A; Beck-Fruchter, R; Golan, J; Lavee, M; Geslevich, Y; Shalev, E

    2016-03-23

    In-vitro fertilization is a known risk factor for ectopic pregnancies. We sought to establish the risk factors for ectopic pregnancy in GnRH antagonist cycles examining patient and stimulation parameters with an emphasis on ovulation trigger. We conducted a retrospective, cohort study of 343 patients undergoing 380 assisted reproductive technology (ART) cycles with the GnRH antagonist protocol and achieving a clinical pregnancy from November 2010 through December 2015. Significant risk factors for ectopic pregnancy in the univariate analysis included prior Cesarean section (CS), endometriosis, mechanical factor infertility, longer stimulation, elevated estradiol and progesterone levels, GnRH agonist trigger, higher number of oocytes aspirated, and insemination technique. Independent risk factors for ectopic pregnancy in the multivariate analysis included GnRH agonist trigger, higher number of oocytes aspirated, insemination technique, and prior Cesarean section. Excessive ovarian response, IVF (as opposed to ICSI), prior Cesarean section and GnRH agonist trigger were found to be independent risk factors for ectopic pregnancy. Caution should be exercised before incorporating the GnRH agonist trigger for indications other than preventing OHSS. When excessive ovarian response leads to utilization of GnRH agonist trigger, strategies for preventing ectopic pregnancy, such as a freeze all policy or blastocyst transfer, should be considered. Further studies should elucidate whether adjusting the luteal support can reduce the ectopic pregnancy risk.

  9. Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

    Energy Technology Data Exchange (ETDEWEB)

    Faraco, J.; Francke, U.; Toledo, S. [Stanford Univ. School of Medicine, CA (United States)

    1994-09-01

    Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individuals from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.

  10. GnRH neurons on LSD: a year of rejecting hypotheses that may have made Karl Popper proud.

    Science.gov (United States)

    Moenter, Suzanne M

    2017-11-08

    Gonadotropin-releasing hormone (GnRH) neurons are critical to many aspects of fertility regulation, from producing episodic release critical to both sexes, to providing a central signal to induce the ovulatory cascade in females. This year saw progress through the rejection, and occasional support, of hypotheses in understanding how GnRH neurons contribute to these processes. This brief review provides one laboratory's view of new insights into possible roles for these cells in development, adult reproductive function, and what may go wrong with GnRH neurons in some cases of infertility. Copyright © 2017 Endocrine Society.

  11. Reproductive performance of dairy cows with ovarian cysts after different GnRH and cloprostenol treatments.

    Science.gov (United States)

    López-Gatius, F; López-Béjar, M

    2002-10-15

    Cystic ovarian disease is an important cause of reproductive failure and economic loss for the dairy industry. This report describes two consecutive studies. The objective of the first was to evaluate the response of cows with ovarian cysts to two therapeutic treatments. In the second study, we compared the effectiveness of the best treatment established in Study 1 with that of the Ovsynch protocol. For Study 1, cows were considered to have an ovarian cyst if it was possible to observe a single follicular structure with a follicular antrum diameter > 25 min in the absence of a corpus luteum in three ultrasonographic examinations performed at 7 days intervals. At diagnosis (Day 0), cows were assigned to one of two treatment groups. Cows in Group GnRH/CLP (n = 31) were treated with 100 microg GnRH i.m. and 500 microg cloprostenol (CLP) i.m. on Day 14. Cows in Group GnRH-CLP/CLP(n = 32) were treated with 100 microg GnRH i.m. plus 500 microg CLP i.m. on Day 0, and 500 microg CLP i.m. on Day 14. The animals were inseminated at observed estrus and monitored weekly by ultrasonography for 4 weeks or until Al. Cows in the GnRH-CLP/CLP group showed a lower cystic persistence rate (15.6% 41.9%; P 3%; P = 0.02) than those in the GnRH/CLP group. For the second study, 128 cows with ovarian cysts were randomly assigned to one of two treatment groups: cows in Group Ovsynch (n = 64) were treated with 100 microg GnRH i.m. on Day 0, 500 microg CLP on Day 7, and 100 microm GnRH i.m. 36 h later. Cows in this group were inseminated 24 h after the second GnRH dose (Ovsynch protocol). Cows in Group GnRH-CLP/CLP/GnRH (n = 64)were treated as those in the GnRH-CLP/CLP group of Study 1 but received GnRH 32 h after the second CLP treatment and were inseminated 24 h after this. A further group of cows without ovarian cysts inseminated at natural estrus served as the Group Control (n = 64). Cows in the GnRH-CLP/CLP/ GnRH group showed a lower cystic persistence rate (10.9% 17.2%; P 12.5%; P 3

  12. Uric acid association with pulsatile and steady components of central and peripheral blood pressures.

    Science.gov (United States)

    Lepeytre, Fanny; Lavoie, Pierre-Luc; Troyanov, Stéphan; Madore, François; Agharazii, Mohsen; Goupil, Rémi

    2018-03-01

    Whether the cardiovascular risk attributed to elevated uric acid levels may be explained by changes in central and peripheral pulsatile and/or steady blood pressure (BP) components remains controversial. In a cross-sectional analysis of normotensive and untreated hypertensive participants of the CARTaGENE populational cohort, we examined the relationship between uric acid, and both pulsatile and steady components of peripheral and central BP, using sex-stratified linear regressions. Of the 20 004 participants, 10 161 individuals without antihypertensive or uric acid-lowering drugs had valid pulse wave analysis and serum uric acid levels. In multivariate analysis, pulsatile components of BP were not associated with uric acid levels, whereas steady components [mean BP (MBP), peripheral and central DBP] were all associated with higher levels of uric acid levels in women and men (all P uric acid levels but not for MBP-adjusted cSBP. Peripheral and cSBP, which are aggregate measures of pulsatile and steady BP, were also associated with uric acid levels in women (β = 0.063 and 0.072, respectively, both P uric acid levels. Serum uric acid levels appear to be associated with both central and peripheral steady but not pulsatile BP, regardless of sex.

  13. Nutrient Sensing Overrides Somatostatin and Growth Hormone-Releasing Hormone to Control Pulsatile Growth Hormone Release.

    Science.gov (United States)

    Steyn, F J

    2015-07-01

    Pharmacological studies reveal that interactions between hypothalamic inhibitory somatostatin and stimulatory growth hormone-releasing hormone (GHRH) govern pulsatile GH release. However, in vivo analysis of somatostatin and GHRH release into the pituitary portal vasculature and peripheral GH output demonstrates that the withdrawal of somatostatin or the appearance of GHRH into pituitary portal blood does not reliably dictate GH release. Consequently, additional intermediates acting at the level of the hypothalamus and within the anterior pituitary gland are likely to contribute to the release of GH, entraining GH secretory patterns to meet physiological demand. The identification and validation of the actions of such intermediates is particularly important, given that the pattern of GH release defines several of the physiological actions of GH. This review highlights the actions of neuropeptide Y in regulating GH release. It is acknowledged that pulsatile GH release may not occur selectively in response to hypothalamic control of pituitary function. As such, interactions between somatotroph networks, the median eminence and pituitary microvasculature and blood flow, and the emerging role of tanycytes and pericytes as critical regulators of pulsatility are considered. It is argued that collective interactions between the hypothalamus, the median eminence and pituitary vasculature, and structural components within the pituitary gland dictate somatotroph function and thereby pulsatile GH release. These interactions may override hypothalamic somatostatin and GHRH-mediated GH release, and modify pulsatile GH release relative to the peripheral glucose supply, and thereby physiological demand. © 2015 British Society for Neuroendocrinology.

  14. Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

    KAUST Repository

    Zhang, Xiaomei

    2010-03-04

    We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5\\'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin2 and expressed ERa,ERb, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E2 and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A.E2 + P4 treatment for 4 days, alone or followed by GA, had no effect, but E2 + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endo-metrial epithelial cells in vitro. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

  15. Evaluation of the effect of GnRH on follicular ovarian cysts in dairy cows using trans-rectal ultrasonography.

    Science.gov (United States)

    Jou, P; Buckrell, B C; Liptrap, R M; Summerlee, A J; Johnson, W H

    1999-10-01

    The objectives of this study were to evaluate ovarian changes in cows with follicular ovarian cysts following treatment with either GnRH or saline. The parameters determined were the intervals from treatment to observation of a CL and from treatment to disappearance of the cyst, and the association between serum concentrations of LH, FSH and the LH/FSH ratio, before and after treatment, with the test intervals. Thirty-nine cows were identified as having follicular cysts. The GnRH treatment induced a significant increase in LH and the LH/FSH ratio. The gonadotropin response was not associated with the intervals from treatment to CL detection or to disappearance of the cyst. Survival curves for the intervals from treatment to CL detection and cyst disappearance indicate that treatment with GnRH or saline did not yield significantly different results for either parameter. The results question the efficacy of treating cystic ovarian disease with GnRH.

  16. Evidence that GnRH decreases with gonadal steroid feedback but increases with age in postmenopausal women.

    Science.gov (United States)

    Gill, Sabrina; Sharpless, Julie L; Rado, Kimberly; Hall, Janet E

    2002-05-01

    Studies of the effects of gonadal steroid negative feedback and age on the hypothalamic-pituitary axis in postmenopausal women (PMW) have identified significant but inconsistent changes in gonadotropin dynamics. In the current study, we investigated the effect of gonadal steroid replacement and age on overall GnRH secretion estimated by using submaximal GnRH receptor blockade. Twenty-four healthy PMW, 45-55 yr (n = 13) and 70-80 yr (n = 11), were studied. Subjects were studied at baseline (BL) on no hormone replacement therapy, after 1 month of transdermal estrogen (50 microg/d; E) and again after a further month of E and 7 d of transvaginal progesterone (100 mg bid; E + P). At each admission, blood was sampled every 30 min for 4 (BL and E) or 8 h (E + P) before and 10 h after sc administration of a submaximal dose (5 microg/kg) of the NAL-GLU GnRH antagonist ([Ac-D2Nal(1), D4ClPhe(2), DPal(3), Arg(5), DGlu(AA)(6), DAla(10)] GnRH). Percent inhibition of LH was calculated by expressing the difference between the nadir following GnRH antagonist administration and the preantagonist baseline as a percent of the baseline. Physiologic E and P levels were achieved with the appropriate hormone replacement regimens. Mean LH levels decreased from baseline with E alone and decreased further with E + P (81.4 +/- 6.6, 68.2 +/- 8.1 and 48.0 +/- 4.3 IU/liter, respectively; P < 0.005). Percent inhibition of LH following submaximal GnRH receptor blockade decreased with age (57.6 +/- 1.8% in young PMW vs. 51.4 +/-2.2% in old PMW; P < 0.05) implying an increase in GnRH secretion with age. There was an increase in percent inhibition of LH in response to submaximal GnRH receptor blockade with E and a further increase with E + P (54.8 +/-1.5%, 58.8 +/- 1.9% and 69.9 +/- 2.8%, respectively; P < 0.05), indicating a progressive decrease in endogenous GnRH secretion with gonadal steroid feedback. Mean LH and FSH levels were lower at baseline in old compared with young PMW. However, the

  17. Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release

    DEFF Research Database (Denmark)

    Ansel, L; Bentsen, A H; Ancel, C

    2011-01-01

    In seasonal breeders, reproduction is synchronised by day length via the pineal hormone melatonin. In short winter days (short day, SD), the Syrian hamster displays a complete gonadal atrophy together with a marked reduction in expression of kisspeptins (Kp), a family of potent hypothalamic...... stimulators of GNRH neurons. Both central and peripheral acute injections of Kp have been reported to activate the gonadotropic axis in mammals. The aim of this study was to determine if and how peripheral administration of Kp54 could restore gonadal function in photo-inhibited hamsters. Testicular activity...... of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong increase...

  18. Enhanced incorporation of nonhydrolyzable tritium in GnRH and TRF by catalytic exchange labeling

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, J.; Bienert, M.; Niedrich, H.; Mittag, E.; Toth, G.

    1987-12-01

    Gonadotropin releasing hormone (GnRH), D-Phe/sub 6/-GnRH and thyro-tropin releasing factor (TRF) were tritiated by direct catalytic exchange using RhA1/sub 2/O/sub 3/ + HT under conditions which lead in model deuterations of N..cap alpha..-acetylhistidine amide to a high incorporation of deuterium into position 5 of the histidine ring. Specific activities up to a range of 400 GBqmmol in form of nonhydrolyzable tritium are attainable after removal of the label incorporated into position 2 of the histidine ring. A crucial reason for diminished specific activities was found to be a catalyst mediated hydrogen transfer between the peptides and traces of water, contained in the reaction mixture, competing with the tritiation.

  19. GnRH receptors in human granulosa cells: Anatomical localization and characterization by autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Latouche, J.; Crumeyrolle-Arias, M.; Jordan, D.; Kopp, N.; Augendre-Ferrante, B.; Cedard, L.; Haour, F. (Institut Pasteur, Paris (France))

    1989-09-01

    The presence of receptors for GnRH in human ovary has been investigated by quantitative autoradiography. Simultaneous visualization and characterization of specific receptors on frozen sections were obtained on six pairs of human ovaries. Among them only one exhibited a large preovulatory follicle. This dominant follicle exhibited a specific and high affinity binding capacity for {sup 125}I-GnRHa exclusively localized on the granulosa cell layer. Analysis of saturation curve indicates a Kd value of 0.22 nM and Bmax of 9.6 fmol/mg protein. In contrast LH-hCG binding sites were present in all antral follicles. These data demonstrate for the first time the presence of high affinity GnRH receptors in human granulosa cells at a late stage of follicular maturation.

  20. Quantitative flow and velocity measurements of pulsatile blood flow with 4D-DSA

    Science.gov (United States)

    Shaughnessy, Gabe; Hoffman, Carson; Schafer, Sebastian; Mistretta, Charles A.; Strother, Charles M.

    2017-03-01

    Time resolved 3D angiographic data from 4D DSA provides a unique environment to explore physical properties of blood flow. Utilizing the pulsatility of the contrast waveform, the Fourier components can be used to track the waveform motion through vessels. Areas of strong pulsatility are determined through the FFT power spectrum. Using this method, we find an accuracy from 4D-DSA flow measurements within 7.6% and 6.8% RMSE of ICA PCVIPR and phantom flow probe validation measurements, respectively. The availability of velocity and flow information with fast acquisition could provide a more quantitative approach to treatment planning and evaluation in interventional radiology.

  1. The Characteristics of Turbulence in Curved Pipes under Highly Pulsatile Flow Conditions

    Science.gov (United States)

    Kalpakli, A.; Örlü, R.; Tillmark, N.; Alfredsson, P. Henrik

    High speed stereoscopic particle image velocimetry has been employed to provide unique data from a steady and highly pulsatile turbulent flow at the exit of a 90 degree pipe bend. Both the unsteady behaviour of the Dean cells under steady conditions, the so called "swirl switching" phenomenon, as well as the secondary flow under pulsations have been reconstructed through proper orthogonal decomposition. The present data set constitutes - to the authors' knowledge - the first detailed investigation of a turbulent, pulsatile flow through a pipe bend.

  2. Kisspeptin Activates Ankrd 26 Gene Expression in Migrating Embryonic GnRH Neurons

    Directory of Open Access Journals (Sweden)

    Tomoko eSoga

    2016-03-01

    Full Text Available Kisspeptin, a newly discovered neuropeptide regulates gonadotropin-releasing hormone (GnRH. Kisspeptins are a large RF-amide family of peptides. The kisspeptin coded by kiss1 gene is a 145-amino acid- protein that is cleaved to C-terminal peptide kisspeptin-10. G-protein coupled receptor 54 (GPR54 has been identified as a kisspeptin receptor, and it is expressed in GnRH neurons and in a variety of cancer cells. In this study, enhanced green fluorescent protein (EGFP labelled GnRH cells with migratory properties, which express GPR54, served as a model to study the effects of kisspeptin on cell migration. We monitored EGFP–GnRH neuronal migration in brain slide culture of embryonic day 14 transgenic rat by live cell imaging system and studied the effects of kisspeptin-10 (1nM treatment for 36h on GnRH migration. Furthermore to determine kisspeptin-induced molecular pathways related with apoptosis, and cytoskeletal changes during neuronal migration, we studied the expression levels of candidate genes in laser captured EGFP–GnRH neurons by real time PCR. We found that there was no change in the expression level of genes related to cell proliferation and apoptosis. The expression of ankyrin repeat domain-containing protein (ankrd 26 in EGFP–GnRH neurons was up-regulated by the exposure to kisspeptin. These studies suggest that ankrd26 gene plays an unidentified role in regulating neuronal movement mediated by kisspeptin-GPR54 signaling, which could be a potential pathway to suppress cell migration.

  3. Kisspeptin Activates Ankrd 26 Gene Expression in Migrating Embryonic GnRH Neurons

    Science.gov (United States)

    Soga, Tomoko; Lim, Wei Ling; Khoo, Alan Soo-Beng; Parhar, Ishwar S.

    2016-01-01

    Kisspeptin, a newly discovered neuropeptide, regulates gonadotropin-releasing hormone (GnRH). Kisspeptins are a large RF-amide family of peptides. The kisspeptin coded by KiSS-1 gene is a 145-amino acid protein that is cleaved to C-terminal peptide kisspeptin-10. G-protein-coupled receptor 54 (GPR54) has been identified as a kisspeptin receptor, and it is expressed in GnRH neurons and in a variety of cancer cells. In this study, enhanced green fluorescent protein (EGFP) labeled GnRH cells with migratory properties, which express GPR54, served as a model to study the effects of kisspeptin on cell migration. We monitored EGFP–GnRH neuronal migration in brain slide culture of embryonic day 14 transgenic rat by live cell imaging system and studied the effects of kisspeptin-10 (1 nM) treatment for 36 h on GnRH migration. Furthermore, to determine kisspeptin-induced molecular pathways related with apoptosis and cytoskeletal changes during neuronal migration, we studied the expression levels of candidate genes in laser-captured EGFP–GnRH neurons by real-time PCR. We found that there was no change in the expression level of genes related to cell proliferation and apoptosis. The expression of ankyrin repeat domain-containing protein (ankrd) 26 in EGFP–GnRH neurons was upregulated by the exposure to kisspeptin. These studies suggest that ankrd 26 gene plays an unidentified role in regulating neuronal movement mediated by kisspeptin–GPR54 signaling, which could be a potential pathway to suppress cell migration. PMID:26973595

  4. Corifollitropin alfa in a long GnRH agonist protocol: proof of concept trial.

    Science.gov (United States)

    Fatemi, Human M; Oberyé, Janine; Popovic-Todorovic, Biljana; Witjes, Han; Mannaerts, Bernadette; Devroey, Paul

    2010-10-01

    Fifty healthy women, aged 18-39 years with no known risk of ovarian hyperstimulation were treated with 100 or 150 μg corifollitropin alfa (dependent on body weight) in a long GnRH agonist protocol. At these doses, corifollitropin alfa initiated and supported growth of a large cohort of follicles during the first week of ovarian stimulation. Copyright © 2010. Published by Elsevier Inc.

  5. GnRH agonist for triggering of final oocyte maturation: time for a change of practice?

    DEFF Research Database (Denmark)

    Humaidan, P; Kol, Stefan; Papanikolaou, E G

    2011-01-01

    GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase...... deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering....

  6. GnRH agonist trigger versus hCG trigger in GnRH antagonist in IVF/ICSI cycles: A review article

    Directory of Open Access Journals (Sweden)

    Ashraf Alyasin

    2016-09-01

    Full Text Available Routinely, a bolus of 5.000-10.000 IU human chorionic gonadotropin (hCG is used for the final follicular maturation and ovulation as a standard method. HCG has the same effect of luteinizing hormone (LH with long half-life. It has the long lutheotrophic effect which increases the risk of ovarian hyper stimulation syndrome (OHSS. Recently, gonadotropin-releasing hormone agonist (GnRH-a trigger has been used for the induction of final follicular maturation and ovulation with the aim of reducing the OHSS risk. Several studies have shown that the releases of endogenous follicular stimulating hormone (FSH and LH after administration of GnRH agonist in in vitro fertilization (IVF cycles are able to precede the final follicular maturation leading to removal of fertile oocyte with normal development of the embryo and ultimately pregnancy. But based on the results of some studies, using GnRH-a trigger leads to defect luteal-phase resulting to reduce the implantation and clinical pregnancy rates and also increase abortion in fresh embryo transfer cycles compared to routine IVF cycle with hCG triggering . Also, in recent years, studies have continued to modify the luteal phase support, so that the fresh embryo transfer is possible too. In this review, we examined the benefits, problems, and also ways to reform GnRH agonist triggering complications.

  7. Bovine ovarian follicular cysts: in vitro effects of lecirelin, a GnRH analogue.

    Science.gov (United States)

    Rizzo, Annalisa; Cosola, Claudia; Mutinati, Maddalena; Spedicato, Massimo; Minoia, Giuseppe; Sciorsci, Raffaele Luigi

    2010-12-01

    This study investigates the mechanisms of action by which a GnRH analogue may modulate the contractility of the bovine ovarian follicular wall. The in vitro evaluation of the spontaneous basal contractility of bovine preovulatory and cystic follicles was performed, followed by testing the effects of lecirelin, a GnRH analogue, on their basal contractility. Strips of tissue in isolated organ bath were employed. In addition, to better investigate the mechanism of action of lecirelin, the study of the effects of cumulative doses of nifedipine (a calcium channel blocker), phentolamine (an α-adrenoceptor antagonist) and reserpine (an inhibitor of the vesicular up-take of catecholamines) alone and, at the highest doses employed, associated to lecirelin, was set up. The results demonstrate that in basal conditions and after the addition of lecirelin, the strips from preovulatory follicles contract significantly more than strips from cysts. Furthermore, among the patterns of contractility evoked by the three drugs employed, the one induced by nifedipine was the only one unaffected by the addition of lecirelin. The data obtained provide the hypothesis that one of the main mechanisms of action of GnRH, could involve calcium channels. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Study of Positive and Negative Consequences of Using GnRH Antagonist in Intrauterine Insemination Cycles

    Directory of Open Access Journals (Sweden)

    Maryam Bagheri

    2009-01-01

    Full Text Available Background: To assess the usefulness of premature luteinization hormone (LH surge preventionin an intrauterine insemination (IUI cycle by GnRH antagonist administration.Materials and Methods: Sixty patients with unexplained or mild male infertility or minimalto mild endometriosis were enrolled in this prospective randomized controlled trial. There weretwenty patients in group A (with GnRH antagonist and 40 patients in group B (without GnRHantagonist.In all of the participants, clomiphene citrate and human menopausal gonadotropin (CC+HMG wereused for ovarian stimulation. When at least one follicle with ≥ 16 mm diameter was seen, LH surgewas checked by a urinary LH kit. In patients with negative results, human chorionic gonadotropinwas continued in both groups, but in group A 0.25 mg Ganirelix SQ was administered for two days,,then in both groups human chorionic gonadotropin (HCG was injected on the third day and IUIwas done 36-40 hours later. Ongoing pregnancy was the primary outcome.Results: Baseline characters and clinical parameters were similar in both groups with the exceptionof ≥14 mm follicles which were higher in group A (p value= 0.003. The pregnancy rate in bothgroups was not significantly different, although it was higher in group B (10% in group A and 15%in group B.Conclusion: At least in CC+HMG stimulated cycles for IUI, the occurrence of premature LHsurge could have a useful rule and GnRH antagonist administration could be an inappropriateintervention.

  9. Effect of Deletion of Ghrelin-O-Acyltransferase on the Pulsatile Release of Growth Hormone in Mice.

    Science.gov (United States)

    Xie, T Y; Ngo, S T; Veldhuis, J D; Jeffery, P L; Chopin, L K; Tschöp, M; Waters, M J; Tolle, V; Epelbaum, J; Chen, C; Steyn, F J

    2015-12-01

    Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat(-/-) mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat(-/-) mice compared to age-matched wild-type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of insulin-like growth factor (IGF)-1 were elevated in goat(-/-) mice. This rise in circulating levels of IGF-1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF-1 release in goat(-/-) mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of

  10. Transrectal ultrasonic diagnosis of ovarian follicular cysts in goats and treatment with GnRH.

    Science.gov (United States)

    Medan, M S; Watanabe, G; Sasaki, K; Taya, K

    2004-08-01

    Cystic ovarian disease is an important cause of reproductive failure. The objective of this study was to evaluate transrectal ultrasonography as a diagnostic tool and gonadotropin-releasing hormone (GnRH) as a therapeutic approach for ovarian follicular cysts in goats. Goats were considered to have a follicular cyst(s) if a non-echoic structure >10 mm in diameter was detected in the absence of corpora lutea (CL) in three ultrasonic examinations performed at 5-day intervals. After diagnosis (Day 0), goats with ovarian follicular cysts (n = 5) were treated with a single bolus injection of 10.5 microg synthetic GnRH followed by administration of 125 microg prostaglandin F2alpha (PGF2alpha) 10 days later. Five blood samples were collected at 5-day intervals for determination of progesterone and estradiol-17beta. For detection of LH surge, blood samples were collected every 2 h. Ovulation rate was determined and pregnancy was confirmed by transrectal ultrasonography. The results showed that transrectal ultrasonography is reliable for diagnosis of ovarian follicular cysts and the mean diameter of the follicular cysts was 12.6 +/- 0.4 mm. Plasma concentrations of progesterone and estradiol-17beta at the time of diagnosis of follicular cysts (Day 0) were 0.7 +/- 0.2 ng/ml and 12.7 +/- 0.9 pg/ml, respectively. The concentration of progesterone increased to 4.0 +/- 0.5 ng/ml 10 days after administration of GnRH indicating luteinization of the ovarian follicular cysts concomitant with a decrease in the concentration of estradiol-17beta (3.5 +/- 0.4 pg/ml). Administration of GnRH to cystic goats resulted in a surge of LH within 2 h of treatment. The interval from PGF2alpha injection to the preovulatory LH surge was 62.8 +/- 1.4 h. All goats exhibited estrus 55.2 +/- 2.3 h after PGF2alpha injection and four goats out of the five ovulated. The ovulation rate was 1.5 +/- 0.3. In conclusion, results of this study suggest that transrectal ultrasonography is a reliable tool for

  11. Chloride Accumulators NKCC1 and AE2 in Mouse GnRH Neurons: Implications for GABAA Mediated Excitation.

    Directory of Open Access Journals (Sweden)

    Carol Taylor-Burds

    Full Text Available A developmental "switch" in chloride transporters occurs in most neurons resulting in GABAA mediated hyperpolarization in the adult. However, several neuronal cell subtypes maintain primarily depolarizing responses to GABAA receptor activation. Among this group are gonadotropin-releasing hormone-1 (GnRH neurons, which control puberty and reproduction. NKCC1 is the primary chloride accumulator in neurons, expressed at high levels early in development and contributes to depolarization after GABAA receptor activation. In contrast, KCC2 is the primary chloride extruder in neurons, expressed at high levels in the adult and contributes to hyperpolarization after GABAA receptor activation. Anion exchangers (AEs are also potential modulators of responses to GABAA activation since they accumulate chloride and extrude bicarbonate. To evaluate the mechanism(s underlying GABAA mediated depolarization, GnRH neurons were analyzed for 1 expression of chloride transporters and AEs in embryonic, pre-pubertal, and adult mice 2 responses to GABAA receptor activation in NKCC1-/- mice and 3 function of AEs in these responses. At all ages, GnRH neurons were immunopositive for NKCC1 and AE2 but not KCC2 or AE3. Using explants, calcium imaging and gramicidin perforated patch clamp techniques we found that GnRH neurons from NKCC1-/- mice retained relatively normal responses to the GABAA agonist muscimol. However, acute pharmacological inhibition of NKCC1 with bumetanide eliminated the depolarization/calcium response to muscimol in 40% of GnRH neurons from WT mice. In the remaining GnRH neurons, HCO3- mediated mechanisms accounted for the remaining calcium responses to muscimol. Collectively these data reveal mechanisms responsible for maintaining depolarizing GABAA mediated transmission in GnRH neurons.

  12. Exogenous Kisspeptin Administration as a Probe of GnRH Neuronal Function in Patients With Idiopathic Hypogonadotropic Hypogonadism

    Science.gov (United States)

    Chan, Yee-Ming; Lippincott, Margaret F.; Butler, James P.; Sidhoum, Valerie F.; Li, Cindy X.; Plummer, Lacey

    2014-01-01

    Context: Idiopathic hypogonadotropic hypogonadism (IHH) results from defective synthesis, secretion, or action of GnRH. Kisspeptin is a potent stimulus for GnRH secretion. Objective: We probed the functional capacity of the GnRH neuronal network in patients with IHH. Participants: Eleven subjects with congenital IHH (9 men and 2 women) and one male subject who underwent reversal of IHH were studied. Six of the twelve subjects had an identified genetic cause of their IHH: KAL1 (n = 1), FGFR1 (n = 3), PROKR2 (n = 1), GNRHR (n = 1). Intervention: Subjects underwent q10 min blood sampling to measure GnRH-induced LH secretion at baseline and in response to intravenous boluses of kisspeptin (0.24 nmol/kg) and GnRH (75 ng/kg) both pre- and post-six days of treatment with exogenous GnRH (25 ng/kg sc every 2 h). Results: All subjects with abiding IHH failed to demonstrate a GnRH-induced LH response to exogenous kisspeptin. In contrast, the subject who achieved reversal of his hypogonadotropism demonstrated a robust response to kisspeptin. Conclusions: The functional capacity of the GnRH neuronal network in IHH patients is impaired, as evidenced by their inability to respond to the same dose of kisspeptin that effects a robust GnRH-induced LH response in healthy men and luteal-phase women. This impairment is observed across a range of genotypes, suggesting that it reflects a fundamental property of GnRH neuronal networks that have not been properly engaged during pubertal development. In contrast, a patient who had experienced reversal of his hypogonadotropism responded to exogenous kisspeptin. PMID:25226293

  13. In silico and in situ characterization of the zebrafish (Danio rerio gnrh3 (sGnRH gene

    Directory of Open Access Journals (Sweden)

    Husebye Harald

    2002-08-01

    Full Text Available Abstract Background Gonadotropin releasing hormone (GnRH is responsible for stimulation of gonadotropic hormone (GtH in the hypothalamus-pituitary-gonadal axis (HPG. The regulatory mechanisms responsible for brain specificity make the promoter attractive for in silico analysis and reporter gene studies in zebrafish (Danio rerio. Results We have characterized a zebrafish [Trp7, Leu8] or salmon (s GnRH variant, gnrh3. The gene includes a 1.6 Kb upstream regulatory region and displays the conserved structure of 4 exons and 3 introns, as seen in other species. An in silico defined enhancer at -976 in the zebrafish promoter, containing adjacent binding sites for Oct-1, CREB and Sp1, was predicted in 2 mammalian and 5 teleost GnRH promoters. Reporter gene studies confirmed the importance of this enhancer for cell specific expression in zebrafish. Interestingly the promoter of human GnRH-I, known as mammalian GnRH (mGnRH, was shown capable of driving cell specific reporter gene expression in transgenic zebrafish. Conclusions The characterized zebrafish Gnrh3 decapeptide exhibits complete homology to the Atlantic salmon (Salmo salar GnRH-III variant. In silico analysis of mammalian and teleost GnRH promoters revealed a conserved enhancer possessing binding sites for Oct-1, CREB and Sp1. Transgenic and transient reporter gene expression in zebrafish larvae, confirmed the importance of the in silico defined zebrafish enhancer at -976. The capability of the human GnRH-I promoter of directing cell specific reporter gene expression in zebrafish supports orthology between GnRH-I and GnRH-III.

  14. Single dose and pulsatile treatment with human growth hormone in growth hormone deficiency.

    OpenAIRE

    Smith, P J; Pringle, P J; Brook, C G

    1987-01-01

    The growth and growth hormone profiles in four children receiving three different regimens of treatment with human growth hormone (hGH) were compared. There was no significant difference in the rate of growth between the regimens; the rate of growth fell dramatically after treatment. Pulsatile administration of hGH was no better than conventional treatment.

  15. Development of a new introduction technique for the pulsatile catheter pump

    NARCIS (Netherlands)

    Mihaylov, D; Kik, C; Elstrodt, J; Verkerke, GJ; Blanksma, PK; Rakhorst, G

    The pulsatile catheter (PUCA) pump is an intraventricular blood pump that can be introduced into the left ventricular cavity through a superficial artery (trans arterially) or directly through the thoracic aorta during open chest conditions. When positioned, the pump aspirates blood from the left

  16. Calcium responses of endothelial cell monolayers subjected to pulsatile and steady laminar flow differ.

    Science.gov (United States)

    Helmlinger, G; Berk, B C; Nerem, R M

    1995-08-01

    The vascular endothelium is the primary transducer of hemodynamically imposed mechanochemical events. In this study, we measured the intracellular free calcium concentration ([Ca2+]i) using the fluorescent probe fura 2 and ratiometric digital imaging in cultured bovine aortic endothelial cells (BAEC) subjected to various laminar flow patterns. These were steady shear stress (0.2-70 dyn/cm2) and three types of sinusoidal pulsatile shear stress (nonreversing: 40 +/- 20 dyn/cm2; reversing: 20 +/- 40 dyn/cm2; and purely oscillatory: 0 +/- 20 dyn/cm2; flow frequencies: 0.4, 1.0, and 2.0 Hz) in a serum-containing medium. The most dramatic finding was failure of a purely oscillatory flow to increase [Ca2+]i in BAEC monolayers. In contrast, steady flow, as well as nonreversing and reversing pulsatile flows, increased [Ca2+]i. The dynamics of the response were dependent on the flow pattern. Both internal Ca2+ release and extracellular Ca2+ entry were involved in these [Ca2+]i increases. Also, switching from either a steady nonreversing pulsatile or reversing pulsatile flow back to a static condition resulted in a [Ca2+]i increase. However, switching from an oscillatory flow to a static condition did not induce any changes in average [Ca2+]i. This study shows that endothelial cells are able to sense different flow environments in terms of [Ca2+]i signaling and is relevant to further studies of the influence of hemodynamic forces on vascular pathophysiology.

  17. Tolerance to continuous intrathecal baclofen infusion can be reversed by pulsatile bolus infusion

    NARCIS (Netherlands)

    Heetla, H. W.; Staal, M. J.; van Laar, T.

    Study design: Pilot study. Objective: To study the effect of pulsatile bolus infusion of intrathecal baclofen (ITB) on daily ITB dose, in patients showing dose increases, probably due to tolerance. Setting: Department of neurology and neurosurgery, University Medical Center Groningen, the

  18. Analytical and experimental characterization of a miniature calorimetric sensor in a pulsatile flow

    NARCIS (Netherlands)

    Gelderblom, Hanneke; van der Horst, A.; Haartsen, J.R.; Rutten, M.C.M.; van de Ven, A.A.F.; van de Vosse, F.N.

    2010-01-01

    The behaviour of a miniature calorimetric sensor, which is under consideration for catheter-based coronary-artery-flow assessment, is investigated in both steady and pulsatile tube flows. The sensor is composed of a heating element operated at constant power and two thermopiles that measure

  19. Pulsatile protein release from monodisperse liquid-core microcapsules of controllable shell thickness

    Science.gov (United States)

    Xia, Yujie; Pack, Daniel W.

    2014-01-01

    Purpose Pulsatile delivery of proteins, in which release occurs over a short time after a period of little or no release, is desirable for many applications. This paper investigates the effect of biodegradable polymer shell thickness on pulsatile protein release from biodegradable polymer microcapsules. Methods Using precision particle fabrication (PPF) technology, monodisperse microcapsules were fabricated encapsulating bovine serum albumin (BSA) in a liquid core surrounded by a drug-free poly(lactide-co-glycolide) (PLG) shell of uniform, controlled thickness from 14 to 19 μm. Results When using high molecular weight PLG (Mw 88 kDa), microparticles exhibited the desired core-shell structure with high BSA loading and encapsulation efficiency (55-65%). These particles exhibited very slow release of BSA for several weeks followed by rapid release of 80-90% of the encapsulated BSA within seven days. Importantly, with increasing shell thickness the starting time of the pulsatile release could be controlled from 25 to 35 days. Conclusions Biodegradable polymer microcapsules with precisely controlled shell thickness provide pulsatile release with enhanced control of release profiles. PMID:24831313

  20. Tissue Doppler Imaging in the evaluation of abdominal aortic pulsatility: a useful tool for the neonatologist.

    Science.gov (United States)

    Valerio, Enrico; Grison, Alessandra; Capretta, Anna; Golin, Rosanna; Ferrarese, Paola; Bellettato, Massimo

    2017-03-01

    Sonographic cardiac evaluation of newborns with suspected aortic coarctation (AoC) should tend to demonstrate a good phasic and pulsatile flow and the absence of pressure gradient along a normally conformed aortic arch from the modified left parasternal and suprasternal echocardiographic views; these findings, however, may not necessarily rule out a more distal coarctation in the descending aorta. For this reason, the sonographic exam of newborns with suspected AoC should always include a Doppler evaluation of abdominal aortic blood flow from the subcostal view. Occasionally, however, a clearly pulsatile Doppler flow trace in abdominal aorta may be difficult to obtain due to the bad insonation angle existing between the probe and the vessel. In such suboptimal ultrasonic alignment situation, the use of Tissue Doppler Imaging instead of classic Doppler flow imaging may reveal a preserved aortic pulsatility by sampling the aortic wall motion induced by normal flow. We propose to take advantage of the TDI pattern as a surrogate of a normal pulsatile Doppler flow trace in abdominal aorta when the latter is difficult to obtain due to malalignment with the insonated vessel.

  1. Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man

    Energy Technology Data Exchange (ETDEWEB)

    Paolisso, G.; Scheen, A.J.; Luyckx, A.S.; Lefebvre, P.J.

    1987-01-01

    To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin, basal insulin secretion was replaced by a continuous insulin infusion, and glucagon was infused intravenously in two conditions at random: either continuously or intermittently. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-(3-/sup 3/H)glucose infusion allowed the authors to study glucose turnover. While basal plasma glucagon levels were similar in both conditions, they plateaued at 189 +/- 38 pg ml/sup -1/ during continuous infusion and varied between 95 and 501 pg x ml/sup -1/ during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion 1) initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, 2) did not prevent the so-called evanescent effect of glucagon on blood glucose, and 3) after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucanemia in normal man fails to increase hepatic glucose production.

  2. Pulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells

    DEFF Research Database (Denmark)

    Thilo, Florian; Vorderwülbecke, Bernd J; Marki, Alex

    2012-01-01

    The goal of the study was to assess whether pulsatile atheroprone shear stress modulates the expression of transient receptor potential (TRP) channels, TRPC3, TRPC6, TRPM7, and TRPV1 mRNA, in human umbilical vascular endothelial cells. Exposure of cultured vascular endothelial cells to defined...

  3. Effect of pulsatile blood flow on thrombosis potential with a step wall transition.

    Science.gov (United States)

    Corbett, Scott C; Ajdari, Amin; Coskun, Ahmet U; Nayeb-Hashemi, Hamid

    2010-01-01

    It is well known that thrombus can be formed at stagnation regions in blood flow. However, studies of thrombus formation have typically focused on steady state flow. We hypothesize that pulsating flow may reduce persistent stagnation at the sites of low shear stress by decreasing exposure time. In this study, a step-wall transition, which is commonly found on implantable devices, is used as a test bed causing a recirculation vortex. Stagnation at such a step is considered using computational fluid dynamics studies and flow visualization experiments. Parametric studies were performed with varying step height, pulsatility, and velocity. The percentage of time along the wall with shear stresses below a threshold for thrombosis and the total length of wall that maintains contact with stagnant flow throughout the cardiac cycle are calculated. Persistent stagnation occurs at the corner of a step-wall transition in all cases and is observed to decrease with a decrease in step height, an increase in mean velocity, and an increase in pulsatility. Under steady flow conditions, a flow reattachment point resulting from recirculation is observed with expanding steps, whereas a flow separation point is observed with contracting steps. Pulsatility decreases persistent stagnation at the flow separation point with contracting steps, whereas it completely eliminates persistent stagnation at the flow reattachment point with expanding steps. The results of this work conclusively show that stagnation can be reduced by increasing pulsatility and flow velocity and by decreasing step height.

  4. Pulsatile Lavage of Musculoskeletal Wounds Causes Muscle Necrosis and Dystrophic Calcification in a Rat Model.

    Science.gov (United States)

    Chiaramonti, Alexander M; Robertson, Astor D; Nguyen, Thao P; Jaffe, David E; Hanna, E Lex; Holmes, Robert; Barfield, William R; Fourney, William L; Stains, Joseph P; Pellegrini, Vincent D

    2017-11-01

    Adequate irrigation of open musculoskeletal injuries is considered the standard of care to decrease bacterial load and other contaminants. While the benefit of debris removal compared with the risk of further seeding by high-pressure lavage has been studied, the effects of irrigation on muscle have been infrequently reported. Our aim in the present study was to assess relative damage to muscle by pulsatile lavage compared with bulb-syringe irrigation. In an animal model of heterotopic ossification, 24 Sprague-Dawley rats underwent hindlimb blast amputation via detonation of a submerged explosive, with subsequent through-the-knee surgical amputation proximal to the zone of injury. All wounds were irrigated and underwent primary closure. In 12 of the animals, pulsatile lavage (20 psi [138 kPa]) was used as the irrigation method, and in the other 12 animals, bulb-syringe irrigation was performed. A third group of 6 rats did not undergo the blast procedure but instead underwent surgical incision into the left thigh muscle followed by pulsatile lavage. Serial radiographs of the animals were made to monitor the formation of soft-tissue radiopaque lesions until euthanasia at 6 months. Image-guided muscle biopsies were performed at 8 weeks and 6 months (at euthanasia) on representative animals from each group. Histological analysis was performed with hematoxylin and eosin, alizarin red, and von Kossa staining on interval biopsy and postmortem specimens. All animals managed with pulsatile lavage, with or without blast injury, developed soft-tissue radiopaque lesions, whereas no animal that had bulb-syringe irrigation developed these lesions (p = 0.001). Five of the 12 animals that underwent blast amputation with pulsatile lavage experienced wound complications, whereas no animal in the other 2 groups experienced wound complications (p = 0.014). Radiopaque lesions appeared approximately 10 days postoperatively, increased in density until approximately 16 weeks, then

  5. Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia.

    Science.gov (United States)

    Bachelot, Anne; Chakhtoura, Zeina; Plu-Bureau, Geneviève; Coudert, Mathieu; Coussieu, Christiane; Badachi, Yasmina; Dulon, Jérome; Charbit, Beny; Touraine, Philippe

    2012-10-01

    Women with classical congenital adrenal hyperplasia (CAH) exhibit reduced fertility due to several factors including anovulation. This has been attributed to a disturbed gonadotropic axis as in polycystic ovary syndrome (PCOS), but there is no precise evaluation. Our aim was to evaluate the gonadotropic axis and LH pulsatility patterns and to determine factor(s) that could account for the potential abnormality of LH pulsatility. Case/control study. Sixteen CAH women (11 with the salt-wasting form and five with the simple virilizing form), aged from 18 to 40 years, and 16 age-matched women, with regular menstrual cycles (28 ± 3 days), were included. LH pulse patterns over 6 h were determined in patients and controls. No differences were observed between patients and controls in terms of mean LH levels, LH pulse amplitude, or LH frequency. In CAH patients, LH pulsatility patterns were heterogeneous, leading us to perform a clustering analysis of LH data, resulting in a two-cluster partition. Patients in cluster 1 had similar LH pulsatility patterns to the controls. Patients in cluster 2 had: lower LH pulse amplitude and frequency and presented menstrual cycle disturbances more frequently; higher 17-OH progesterone, testosterone, progesterone, and androstenedione levels; and lower FSH levels. LH pulsatility may be normal in CAH women well controlled by hormonal treatment. Undertreatment is responsible for hypogonadotropic hypogonadism, with low LH pulse levels and frequency, but not PCOS. Suppression of progesterone and androgen concentrations during the follicular phase of the menstrual cycle should be a major objective in these patients.

  6. Superior performance of continuous over pulsatile flow ventricular assist devices in the single ventricle circulation: A computational study.

    Science.gov (United States)

    Schmidt, Tyler; Rosenthal, David; Reinhartz, Olaf; Riemer, Kirk; He, Fei; Hsia, Tain-Yen; Marsden, Alison; Kung, Ethan

    2017-02-08

    This study compares the physiological responses of systemic-to-pulmonary shunted single ventricle patients to pulsatile and continuous flow ventricular assist devices (VADs). Performance differences between pulsatile and continuous flow VADs have been clinically observed, but the underlying mechanism remains poorly understood. Six systemic-to-pulmonary shunted single ventricle patients (mean BSA=0.30m(2)) were computationally simulated using a lumped-parameter network tuned to match patient specific clinical data. A first set of simulations compared current clinical implementation of VADs in single ventricle patients. A second set modified pulsatile flow VAD settings with the goal to optimize cardiac output (CO). For all patients, the best-case continuous flow VAD CO was at least 0.99L/min greater than the optimized pulsatile flow VAD CO (p=0.001). The 25 and 50mL pulsatile flow VADs exhibited incomplete filling at higher heart rates that reduced CO as much as 9.7% and 37.3% below expectations respectively. Optimization of pulsatile flow VAD settings did not achieve statistically significant (p<0.05) improvement to CO. Results corroborate clinical experience that continuous flow VADs produce higher CO and superior ventricular unloading in single ventricle patients. Impaired filling leads to performance degradation of pulsatile flow VADs in the single ventricle circulation. Published by Elsevier Ltd.

  7. Increasing awareness with recognition of pulsatile tinnitus for nurse practitioners in the primary care setting: A case study.

    Science.gov (United States)

    Vecchiarelli, Kelly; Amar, Arun Paul; Emanuele, Donna

    2017-09-01

    Pulsatile tinnitus is a whooshing sound heard synchronous with the heartbeat. It is an uncommon symptom affecting fewer than 10% of patients with tinnitus. It often goes unrecognized in the primary care setting. Failure to recognize this symptom can result in a missed or delayed diagnosis of a potentially life-threatening condition known as a dural arteriovenous fistula. The purpose of this case study is to provide a structured approach to the identification of pulsatile tinnitus and provide management recommendations. A case study and review of pertinent literature. Pulsatile tinnitus usually has a vascular treatable cause. A comprehensive history and physical examination will alert the nurse practitioner (NP) when pulsatile tinnitus is present. Auscultation in specific areas of the head can detect audible or objective pulsatile tinnitus. Pulsatile tinnitus that is audible to the examiner is an urgent medical condition requiring immediate consultation and referral. Knowledge of pulsatile tinnitus and awareness of this often treatable condition directs the NP to perform a detailed assessment when patients present with tinnitus, directs appropriate referral for care and treatment, and can reduce the risk of delayed or missed diagnosis. ©2017 American Association of Nurse Practitioners.

  8. Photoaffinity labeling of pituitary GnRH receptors: significance of the position of photolabel on the ligand

    Energy Technology Data Exchange (ETDEWEB)

    Nikolics, K.; Szonyi, E.; Ramachandran, J.

    1988-03-08

    Photoreactive derivatives of GnRH and its analogues were prepared by incorporation of the 2-nitro-4(5)-azidophenylsulfenyl (2,4(5)-NAPS) group into amino acid residues at position 1, 3, 6, or 8 of the decapeptide sequence. The modification of Trp/sup 3/ by the 2,4-NAPS group led to a complete loss of the luteinizing hormone (LH) releasing as well as LH-release-inhibiting activity of the peptide. The (D-Lys(2,4-NAPS))/sup 6/ analog was a very potent agonist that, after covalent attachment by photoaffinity labeling, caused prolonged LH secretion at a submaximal rate. (Orn(2,4-NAPS))/sup 8/-GnRH, a full agonist with a relative potency of 7% of GnRH, after photoaffinity labeling caused prolonged maximal LH release from cultured pituitary cells. In contrast, (Orn(2,5-NAPS))/sup 8/-GnRH, although being equipotent with the 2,4-NAPS isomer in terms of LH releasing ability, was unable to cause prolonged LH release after photoaffinity labeling. Thus, (Orn(2,4-NAPS))/sup 8/GnRH is very effective photolabeling ligand of the functionally significant pituitary GnRH receptor. Based on this compound, a pituitary peptidase resistant derivative, D-Phe/sup 6/, (Orn(2,4-NAPS))/sup 8/-GnRH-(1-9)-ethylamide, was synthesized. This derivative showed high-affinity binding to pituitary membranes with a K/sub d/ comparable to those of other GnRH analogues. A radioiodinated form of this peptide was used for pituitary GnRH-receptor labeling. This derivative labeled 59- and 57-kDa proteins in rat and 58- and 56-kDa proteins in bovine pituitary membrane preparations, respectively. This peptide also labeled pituitary GnRH receptors in the solubilized state and therefore appears to be a suitable ligand for the isolation and further characterization of the receptor.

  9. Effect of estradiol on hypothalamic GnRH and pituitary and serum LH and FSH in ovariectomized pigs.

    Science.gov (United States)

    Cox, N M; Britt, J H

    1982-10-01

    Two experiments were conducted to measure pituitary gonadotropins, hypothalamic-gonadotropin releasing hormone (GnRH) and pituitary response to GnRH during periods when serum luteinizing hormone (LH) was suppressed by estradiol-17 beta (e2) in ovariectomized pigs. In the first experiment, 10 ovariectomized gilts were assigned to two groups of five each according to time of slaughter (24 or 36 h after injection). Within each group, gilts were given corn oil (n = 2) or 400 micrograms E2 (n = 3). Neither serum nor anterior pituitary (AP) concentrations of follicle-stimulating hormone (FSH) were affected by E2. Serum LH was suppressed from 12 to 26 h after E2. Concentrations of LH in AP were unchanged at 24 h, but increased at 36 h after E2 injection. Concentrations of GnRH in medial basal hypothalamus (MBH), stalk-median eminence (SME) and hypophyseal portal area (HPA) were lower at 24 h after E2 than in oil-treated gilts. At 36 h after E2, suppressive effects of E2 on LH in serum had subsided and concentrations of LH in AP and GnRH in MBH and SME were greater than in oil-treated controls. The observation that E2 suppressed LH in serum without a detectable suppression of LH in AP led to the hypothesis that E2 had caused the suppression of serum LH by suppression of GnRH release. In a second experiment, 12 ovariectomized gilts were assigned to receive corn oil (n = 4), 400 micrograms E2 (n = 4) or 400 micrograms E2 plus GnRH (1.5 micrograms/h; n = 4). Patterns of LH in sera of E2-treated animals were similar to those in the first experiment, with serum LH in E2-treated gilts suppressed from 4 to 32 h after treatment. However, in gilts receiving GnRH in addition to E2, serum LH concentrations during 20 to 32 h after treatment were intermediate between gilts receiving E2 alone and controls. Thus the pituitary of the pig is capable of responding to GnRH when LH is normally suppressed by E2. These experiments provide two lines of evidence that suppression of serum LH by E2

  10. Sigmoid Sinus Diverticulum, Dehiscence, and Venous Sinus Stenosis: Potential Causes of Pulsatile Tinnitus in Patients with Idiopathic Intracranial Hypertension?

    Science.gov (United States)

    Lansley, J A; Tucker, W; Eriksen, M R; Riordan-Eva, P; Connor, S E J

    2017-09-01

    Pulsatile tinnitus is experienced by most patients with idiopathic intracranial hypertension. The pathophysiology remains uncertain; however, transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence have been proposed as potential etiologies. We aimed to determine whether the prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence was increased in patients with idiopathic intracranial hypertension and pulsatile tinnitus relative to those without pulsatile tinnitus and a control group. CT vascular studies of patients with idiopathic intracranial hypertension with pulsatile tinnitus (n = 42), without pulsatile tinnitus (n = 37), and controls (n = 75) were independently reviewed for the presence of severe transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence according to published criteria. The prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence in patients with idiopathic intracranial hypertension with pulsatile tinnitus was compared with that in the nonpulsatile tinnitus idiopathic intracranial hypertension group and the control group. Further comparisons included differing degrees of transverse sinus stenosis (50% and 75%), laterality of transverse sinus stenosis/sigmoid sinus diverticulum/dehiscence, and ipsilateral transverse sinus stenosis combined with sigmoid sinus diverticulum/dehiscence. Severe bilateral transverse sinus stenoses were more frequent in patients with idiopathic intracranial hypertension than in controls (P intracranial hypertension group. Sigmoid sinus dehiscence (right- or left-sided) was also more common in patients with idiopathic intracranial hypertension compared with controls (P = .01), but there was no significant association with pulsatile tinnitus within the idiopathic intracranial hypertension group. While our data corroborate previous studies demonstrating increased prevalence of sigmoid sinus diverticulum/dehiscence and transverse sinus stenosis in

  11. Annual gonadal cycles in birds: modeling the effects of photoperiod on seasonal changes in GnRH-1 secretion.

    Science.gov (United States)

    Dawson, Alistair

    2015-04-01

    This paper reviews current knowledge of photoperiod control of GnRH-1 secretion and proposes a model in which two processes act together to regulate GnRH1 secretion. Photo-induction controls GnRH1 secretion and is directly related to prevailing photoperiod. Photo-inhibition, a longer term process, acts through GnRH1 synthesis. It progresses each day during daylight hours, but reverses during darkness. Thus, photo-inhibition gradually increases when photoperiods exceed 12h, and reverses under shorter photoperiods. GnRH1 secretion on any particular day is the net result of these two processes acting in tandem. The only difference between species is their sensitivity to photo-inhibition. This can potentially explain differences in timing and duration of breeding seasons between species, why some species become absolutely photorefractory and others relatively photorefractory, why breeding seasons end at the same time at different latitudes within species, and why experimental protocols sometimes produce results that appear counter to what happens naturally. Copyright © 2014 The Author. Published by Elsevier Inc. All rights reserved.

  12. [The neuroendocrinological and histopathological assessment of normogonadotropic azoospermic patients: the usefulness of the GnRH stimulation test].

    Science.gov (United States)

    Rosete Rossetti, R; Alvarado García, A; Bustos López, H H; Barrón Vallejo, J; Sinibaldi Gómez, J

    1994-10-01

    This study evaluates the effect of gonadotropin releasing hormone (GnRH) administration on serum levels of FSH and LH. Also, relate those results with histopathologic findings of testicular biopsies. This was a prospective, clinical trial with a control group. It was done at Department of Reproductive Biology "20 de Noviembre" Hospital, ISSSTE, México City. Fifteen azoospermic, normogonadotropic patients without testicular atrophy and ten normal men use as control group. A GnRH challenge test was made in both groups, two days after we perform a testicular biopsy in patients with azoospermia. There was no significant difference in serum LH concentrations between the two groups, neither before or after GnRH challenge test. There was a statistical difference between serum FSH values of azoospermic patients, than those of control group, the former with higher values than those of the latter. As worst testicular damage was, we found also a higher FSH value on the GnRH challenge test. The GnRH challenge test perform in azoospermic, normogonadotropic patients is very helpful to detect those patients with gonadal damage. As higher the FSH values were, we found that an abnormal testicular biopsy was also more common.

  13. Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

    Science.gov (United States)

    Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

    2016-01-01

    Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

  14. Pharmacological and toxicological assessment of a potential GnRH vaccine in young-adult male pigs.

    Science.gov (United States)

    Turkstra, J A; van der Staay, F J; Stockhofe-Zurwieden, N; Woelders, H; Meloen, R H; Schuurman, T

    2011-05-12

    Active immunization against gonadotrophin-releasing hormone (GnRH) is successfully applied to prevent boar taint in pork. In men, GnRH immunization could be an alternative to hormone therapy in patients with prostate cancer. In this study, a new GnRH vaccine formulation (a modified GnRH peptide conjugate formulated with CoVaccine adjuvant) was investigated for its pharmacological efficacy and safety in young-adult male pigs. Immunization resulted in castrate-like plasma testosterone levels in all treated pigs from week 8 until the end of the study, 30 weeks after the first immunization. Testosterone depletion retarded testes growth, reduced the relative weight of the testes and accessory sex organs, and reduced sperm counts and motility. There was no clinically relevant toxicity. Typical vaccination-related adverse reactions, such as swelling at the injection site and fever, were considered acceptable. We conclude that this GnRH vaccine efficiently and rapidly reduced serum testosterone levels, without inducing chronic toxic effects, and therefore could be applicable in both veterinary and human medicine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Rostro-caudal maturation of glial cells in the accessory olfactory system during development: involvement in outgrowth of GnRH neurites.

    Science.gov (United States)

    Geller, Sarah; Lomet, Didier; Caraty, Alain; Tillet, Yves; Duittoz, Anne; Vaudin, Pascal

    2017-10-03

    During mammalian embryonic development, GnRH neurones differentiate from the nasal placode and migrate through the nasal septum towards the forebrain. We previously showed that a category of glial cells, the olfactory ensheathing cells (OEC), forms the microenvironment of migrating GnRH neurones. Here, to characterize the quantitative and qualitative importance of this glial, we investigated the spatiotemporal maturation of glial cells in situ and the role of maturing glia in GnRH neurones development ex vivo. More than 90% of migrating GnRH neurones were found to be associated with glial cells. There was no change in the cellular microenvironment of GnRH neurones in the regions crossed during embryonic development as glial cells formed the main microenvironment of these neurones (53.4%). However, the phenotype of OEC associated with GnRH neurones changed across regions. The OEC progenitors immunoreactive to brain lipid binding protein formed the microenvironment of migrating GnRH neurones from the vomeronasal organ to the telencephalon and were also present in the diencephalon. However, during GnRH neurone migration, maturation of OEC to [GFAP+] state (glial fibrillary acid protein) was only observed in the nasal septum. Inducing depletion of OEC in maturation, using transgenic mice expressing herpes simplex virus thymidine kinase driven by the GFAP promoter, had no impact on neurogenesis or on triggering GnRH neurones migration in nasal explant culture. Nevertheless, depletion of [GFAP+] cells decreased GnRH neurites outgrowth by 57.4%. This study suggests that specific maturation of OEC in the nasal septum plays a role in morphological differentiation of GnRH neurones. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. Treatment of Ovarian Cysts in Dairy Cows with Simultaneous Administration of GnRH and PGF2α has no Clear Advantage Over the Use of GnRH Alone

    Directory of Open Access Journals (Sweden)

    Rudowska Małgorzata

    2015-04-01

    Full Text Available The aim of the study was to determine the therapeutic efficacy o f simultaneous administration of GnRH and PGF2α in dairy cows with ovarian cysts. Ovarian cyst-affected dairy cows were divided into two experimental groups: 54 cows treated with GnRH and PGF2α, and 42 cows treated with GnRH alone, whereas 22 untreated cows served as the control group. Clinical response and reproductive performance were evaluated. The cumulative disappearance was better in treated cows than in the control group; however, there were no differences between the treatment groups (92.6; 95.2% vs. 72.3%. The mean interval from calving to conception was not significantly shorter (being so by 29 d in the GnRH/PGF2α group than in the cows treated with GnRH alone (P > 0.05. The intervals from treatment to conception were also similar in these groups. The pregnancy rate in both treated groups was similar (62% and higher than in the control cows (53%. In the cows with luteal cysts, the total pregnancy rate was higher in all experimental groups; however, only in GnRH-treated cows was this difference statistically significant (77.8% vs. 50.0%, P < 0.05. With time after parturition, the pregnancy rate decreased in all groups. In general, the cows treated with GnRH and PGF2α simultaneously displayed a good clinical response and slight improvement in reproductive performance compared to the single-therapy GnRH group; however, this was not fully convincing.

  17. The Interrelationship of Estrogen Receptor and GnRH in a Basal Vertebrate, the Sea Lamprey

    Directory of Open Access Journals (Sweden)

    Stacia A Sower

    2011-10-01

    Full Text Available The hypothalamic-pituitary system is considered to be a vertebrate innovation and seminal event that emerged prior to or during the differentiation of the ancestral agnathans. Lampreys are the earliest evolved vertebrates for which there is a demonstrated neuroendocrine system. Lampreys have three hypothalamic GnRHs (lGnRH-I, -II, and –III and two and possibly three pituitary GnRH receptors involved in mediating reproductive processes. Estradiol is considered to be a major reproductive steroid in both male and female lampreys. The purpose of this study was to investigate estrogen receptor (ER expression in the lamprey brain in adult sea lampreys. Expression of ER mRNA was confirmed in the adult lamprey brain using RT-PCR. Using digoxigenin (DIG-labeled probes, ER expression was shown to yield moderate, but distinct reaction products in specific neuronal nuclei of the lamprey brain, including the olfactory lobe, hypothalamus, habenular area, and hindbrain. Expression of ER in the hypothalamic area of the brain provides evidence of potential interaction between estradiol and GnRH(s, and is consistent with previous evidence showing estrogen feedback on GnRH in adult lamprey brain. Earlier studies have reported that there is a close distribution of GAD (GABA and lamprey GnRH in the preoptic region in adult lampreys. The establishment of a direct estradiol-kisspeptin-GABA-GnRH interaction in lamprey has yet to be determined and will require future functional and co-localization studies. The phylogenetic position of lampreys as a basal vertebrate allows lampreys to be a basis for understanding the molecular evolution of the neuroendocrine system that arose in the vertebrates.

  18. Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial

    Science.gov (United States)

    Checa, Miguel A; Brassesco, Mario; Sastre, Margalida; Gómez, Manuel; Herrero, Julio; Marque, Laura; Brassesco, Arturo; Espinós, Juan José

    2015-01-01

    The aim of this study is to evaluate the feasibility and safety of random-start controlled ovarian hyperstimulation (COH) for emergency fertility preservation, regardless of the phase of the menstrual cycle. A self-controlled pilot clinical trial (NCT01385332) was performed in an acute-care teaching hospital and in two private reproductive centers in Barcelona, Spain. Eleven egg donors participated in the study. Two random-start gonadotropin-releasing hormone (GnRH) antagonist protocols were assessed in which ganirelix was initiated on either day 10 (protocol B) or on day 20 (protocol C) of the menstrual cycle and was continued until estradiol levels were below 60 pg/dL. These protocols were compared with a standard protocol (protocol A). The main outcome of interest was the number of metaphase 2 oocytes retrieved. Results from this study show that the number of mature oocytes retrieved was comparable across the different protocols (14.3±4.6 in the standard protocol versus 13.0±9.1 and 13.2±5.2 in protocols B and C, respectively; values expressed as mean ± standard deviation). The mean number of days needed for a GnRH antagonist to lower estradiol levels, as well as the ongoing pregnancy rates, were also similar when protocols B (stimulation in follicular phase) and C (stimulation on luteal phase) were compared with protocol A (standard stimulation). GnRH antagonists can be effectively used for random-start controlled ovarian hyperstimulation with an ovarian response similar to that of standard protocols, and the antagonists appear suitable for emergency fertility preservation in cancer patients. PMID:25709506

  19. Population pharmacokinetic modeling of a subcutaneous depot for GnRH antagonist degarelix

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Nielsen, Henrik Aalborg

    Purpose. The objective of this study is to develop a population pharmacokinetic (PK) model that describes the subcutaneous (SC) depot formation of gonadotropin-releasing hormone (GnRH) antagonist degarelix, which is being developed for treatment of prostate cancer, exhibiting dose-volume and dose......-concentration dependent absorption. Methods. The PK analysis is made in NONMEM through joint analysis of data from two phase I clinical studies; an intravenous infusion study and a single SC dose escalation study. The SC absorption is modeled using an approximation to Ficks' second law of diffusion out of a spherical...

  20. Population Pharmacokinetic Modeling of a Subcutaneous Depot for GnRH Antagonist Degarelix

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Nielsen, Henrik Aalborg

    2004-01-01

    Purpose. The objective of this study is to develop a population pharmacokinetic (PK) model that describes the subcutaneous (SC) depot formation of gonadotropin-releasing hormone ( GnRH) antagonist degarelix, which is being developed for treatment of prostate cancer, exhibiting dose-volume and dose......-concentration dependent absorption. Methods. The PK analysis is made in NONMEM through joint analysis of data from two phase I clinical studies; an intravenous infusion study and a single SC dose escalation study. The SC absorption is modeled using an approximation to Ficks' second law of diffusion out of a spherical...

  1. Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial

    Directory of Open Access Journals (Sweden)

    Checa MA

    2015-02-01

    Full Text Available Miguel A Checa,1,2 Mario Brassesco,2 Margalida Sastre,1 Manuel Gómez,2 Julio Herrero,3 Laura Marque,3 Arturo Brassesco,2 Juan José Espinós3 1Department of Obstetrics and Gynecology, Parc de Salut Mar, Universitat Autònoma de Barcelona, 2Centro de Infertilidad y Reproducción Humana (CIRH, 3Centro de Reproducción Asistida Sagrada Familia, Clínica Sagrada Familia, Barcelona, Spain Abstract: The aim of this study is to evaluate the feasibility and safety of random-start controlled ovarian hyperstimulation (COH for emergency fertility preservation, regardless of the phase of the menstrual cycle. A self-controlled pilot clinical trial (NCT01385332 was performed in an acute-care teaching hospital and in two private reproductive centers in Barcelona, Spain. Eleven egg donors participated in the study. Two random-start gonadotropin-releasing hormone (GnRH antagonist protocols were assessed in which ganirelix was initiated on either day 10 (protocol B or on day 20 (protocol C of the menstrual cycle and was continued until estradiol levels were below 60 pg/dL. These protocols were compared with a standard protocol (protocol A. The main outcome of interest was the number of metaphase 2 oocytes retrieved. Results from this study show that the number of mature oocytes retrieved was comparable across the different protocols (14.3±4.6 in the standard protocol versus 13.0±9.1 and 13.2±5.2 in protocols B and C, respectively; values expressed as mean ± standard deviation. The mean number of days needed for a GnRH antagonist to lower estradiol levels, as well as the ongoing pregnancy rates, were also similar when protocols B (stimulation in follicular phase and C (stimulation on luteal phase were compared with protocol A (standard stimulation. GnRH antagonists can be effectively used for random-start controlled ovarian hyperstimulation with an ovarian response similar to that of standard protocols, and the antagonists appear suitable for emergency

  2. Ovarian cysts in lactating dairy cows: incidence, response to GnRH, and reproductive performance

    OpenAIRE

    Santos, R.M.; Démetrio, D.G.B.; Vasconcelos, J.L.M.

    2009-01-01

    A incidência de cistos ovarianos, a resposta ao tratamento com GnRH e os efeitos da ocorrência de cisto no desempenho reprodutivo e na taxa de descarte foram determinados em vacas lactantes da raça Holandesa. Vacas lactantes (n=333) foram avaliadas semanalmente por ultrassonografia a partir da quarta semana pós-parto, visando à detecção de corpos lúteos (CL) e de folículos ovarianos maiores que 10mm. Na sétima semana pós-parto, as vacas foram classificadas: em ciclando (n=248; presença de CL ...

  3. Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Devos, Michel; Humaidan, Peter

    2013-01-01

    OBJECTIVE: To identify whether women with poor ovarian response may benefit from treatment with corifollitropin alfa in a GnRH antagonist protocol. DESIGN: Retrospective pilot study. SETTING: University-based tertiary care center. PATIENT(S): Poor ovarian responders fulfilling the Bologna criteria...... developed by European Society for Human Reproduction and Embryology Consensus Group. INTERVENTION(S): Corifollitropin alfa (150 μg) followed by 300 IU rFSH in a GnRH antagonist protocol. MAIN OUTCOME MEASURE(S): Endocrinologic profile and ongoing pregnancy rates. RESULT(S): Among 43 women treated...... compared with a cohort of patients treated during 2011 with the standard protocol for poor responders in our center (short agonist-hMG) (7% vs. 6.3%). CONCLUSION(S): Treatment of poor ovarian responders, as described by the Bologna criteria, with corifollitropin alfa in a GnRH antagonist protocol results...

  4. A preclinical pharmacokinetic/pharmacodynamic approach to determine a dose of GnRH, for treatment of ovarian follicular cyst in cattle.

    Science.gov (United States)

    Monnoyer, S; Guyonnet, J; Toutain, P L

    2004-12-01

    The objective of this study was to explore the value of a preclinical PK/PD approach to determine a gonadotropin-releasing hormone (GnRH) dose in cows using the pituitary LH response as a surrogate endpoint. Using an indirect effect model with stimulation of the LH entry rate, the in vivo basic pharmacodynamic parameters of GnRH were determined. The EC(50) of GnRH was 51 +/- 16 pg/mL, the EC(50) being the GnRH plasma concentration able to produce 50% of the maximum possible stimulation (S(max)) of the hypophysis (S(max) = 48 +/- 13). From individual PK/PD parameters, the ED(50) of GnRH, i.e. the estimated dose of GnRH required to determine half the maximum possible stimulating effect on LH release, was calculated to 62 microg/h per cow. Using the PK/PD model, the GnRH dose required to achieve a selected breakpoint value of 5 ng/mL for maximum LH concentration (surrogate value for LH concentration predicting clinical efficacy for cystic conditions), was 52 +/- 18 microg and for a standard GnRH dose of 100 microg, the mean maximum plasma LH concentration predicted by the model was 7.22 +/- 0.98 ng/mL.

  5. Serum Anti-Müllerian Hormone Levels in Precocious Puberty Girls according to Stage of GnRH Agonist Treatment.

    Science.gov (United States)

    Nam, Hyo Kyoung; Kim, Hye Ryun; Rhie, Young Jun; Lee, Kee Hyoung

    2017-03-01

    Few studies have investigated the long-term effects of gonadotropin-releasing hormone (GnRH) agonist treatment on the reproductive function of central precocious puberty (CPP) girls. In this cross-sectional study, we assessed the ovarian function by analyzing the serum anti-Müllerian hormone (AMH) levels of CPP girls. Our study included 505 CPP girls subdivided into 5 groups according to the GnRH agonist treatment stage: group A (before treatment, n = 98), group B (3 months after initiation, n = 103), group C (12 months after initiation, n = 101), group D (24 months after initiation, n = 101), and group E (6 months after discontinuation, n = 102). We compared the serum AMH levels of the CPP girls with those of 100 bone age-matched controls (before treatment: n = 55; after discontinuation: n = 45). At baseline, the mean AMH level of the CPP girls was 5.9 ± 3.6 ng/mL. The mean AMH level after 3 months of the GnRH agonist treatment was lower (4.7 ± 3.2 ng/mL, P = 0.047) than that at baseline and recovered after 12 months of treatment. Six months after discontinuation, the AMH levels were similar to those at pre-treatment. Before and after the GnRH agonist treatment, the AMH levels were similar to those of the bone age-matched controls. In the precocious puberty girls, the AMH levels based on the GnRH agonist treatment stage were all within the normal reference range. The results of this study suggest that GnRH agonist treatment has no adverse effects on the reproductive function.

  6. Stiffening-induced high pulsatility flow activates endothelial inflammation via a TLR2/NF-κB pathway.

    Directory of Open Access Journals (Sweden)

    Yan Tan

    Full Text Available Stiffening of large arteries is increasingly used as an independent predictor of risk and therapeutic outcome for small artery dysfunction in many diseases including pulmonary hypertension. The molecular mechanisms mediating downstream vascular cell responses to large artery stiffening remain unclear. We hypothesize that high pulsatility flow, induced by large artery stiffening, causes inflammatory responses in downstream pulmonary artery endothelial cells (PAECs through toll-like receptor (TLR pathways. To recapitulate the stiffening effect of large pulmonary arteries that occurs in pulmonary hypertension, ultrathin silicone tubes of variable mechanical stiffness were formulated and were placed in a flow circulatory system. These tubes modulated the simulated cardiac output into pulsatile flows with different pulsatility indices, 0.5 (normal or 1.5 (high. PAECs placed downstream of the tubes were evaluated for their expression of proinflammatory molecules (ICAM-1, VCAM-1, E-selectin and MCP-1, TLR receptors and intracellular NF-κB following flow exposure. Results showed that compared to flow with normal pulsatility, high pulsatility flow induced proinflammatory responses in PAECs, enhanced TLR2 expression but not TLR4, and caused NF-κB activation. Pharmacologic (OxPAPC and siRNA inhibition of TLR2 attenuated high pulsatility flow-induced pro-inflammatory responses and NF-κB activation in PAECs. We also observed that PAECs isolated from small pulmonary arteries of hypertensive animals exhibiting proximal vascular stiffening demonstrated a durable ex-vivo proinflammatory phenotype (increased TLR2, TLR4 and MCP-1 expression. Intralobar PAECs isolated from vessels of IPAH patients also showed increased TLR2. In conclusion, this study demonstrates for the first time that TLR2/NF-κB signaling mediates endothelial inflammation under high pulsatility flow caused by upstream stiffening, but the role of TLR4 in flow pulsatility-mediated endothelial

  7. Jointly Amplified Basal and Pulsatile Growth Hormone (GH) Secretion and Increased Process Irregularity in Women with Anorexia Nervosa

    DEFF Research Database (Denmark)

    Støving, R K; Veldhuis, J D; Flyvbjerg, A

    1999-01-01

    positively correlated to GH secretion rates. Leptin levels were significantly inversely correlated to the pulsatile, but not the basal, GH secretion rate. The present data demonstrate augmented basal as well as pulsatile GH secretion with disruption of the orderliness of the GH release process in AN....... Accordingly, GH secretion in AN probably reflects altered neuroendocrine feedback regulation, e.g. associated with increased hypothalamic GHRH discharge superimposed on reduced hypothalamic somatostatinergic tone....

  8. Backbone metal cyclization: Novel {sup 99m}Tc labeled GnRH analog as potential SPECT molecular imaging agent in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Barda, Yaniv; Cohen, Nasi; Lev, Vered; Ben-Aroya, Nurit; Koch, Yitzhak; Mishani, Eyal; Fridkin, Mati; Gilon, Chaim E-mail: gilon@vms.huji.ac.il

    2004-10-01

    Gonadotropin-releasing hormone (GnRH) is a decapeptide secreted to the pituitary where it binds to specific receptors on the gonadotropes to regulate gonadotropic hormones (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) synthesis and secretion. Specific GnRH receptors are overexpressed in breast, prostatic, ovarian, and other tumors. The aim of this study was to synthesize a cyclic GnRH analog with high affinity to GnRH receptors that can be radiolabeled with {sup 99m}Tc. A precyclic GnRH analog, [Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH (Gn-2), containing two hemi-chelator groups was synthesized. It was cyclized applying the recently reported backbone metal cyclization (BMC) approach, to obtain cyclo(Re(O)1-10)[Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH (cyclo[Re(O)-Gn-2]). For comparative evaluations, Gn-2 was oxidized on-resin to yield cyclo(S-S,1-10)[Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH, (cyclo[S-S-Gn-2]). The binding affinity of cyclo[Re(O)-Gn-2] to rat pituitary membranes showed IC{sub 50} of 50nM, compared to IC{sub 50} = 10 nM in the native GnRH. Cyclo({sup 99m}Tc(O)1-10)[Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH (cyclo[{sup 99m}Tc(O)-Gn-2]) was synthesized from Gn-2 and showed similar chromatographic behavior to its rhenium surrogate.

  9. Melanin-concentrating hormone (MCH) and gonadotropin-releasing hormones (GnRH) in Atlantic cod, Gadus morhua: tissue distributions, early ontogeny and effects of fasting.

    Science.gov (United States)

    Tuziak, Sarah M; Volkoff, Hélène

    2013-12-01

    Melanin-concentrating hormone (MCH) is classically known for its role in regulating teleost fish skin color change for environmental adaptation. Recent evidence suggests that MCH also has appetite-stimulating properties. The gonadotropin-releasing hormone (GnRH) peptide family has dual roles in endocrine control of reproduction and energy status in fish. Atlantic cod (Gadus morhua) are a commercially important aquaculture species inhabiting the shores of Atlantic Canada. In this study, we examine MCH and GnRH transcript expression profiles during early development as well as in central and peripheral tissues and quantify juvenile Atlantic cod MCH and GnRH hypothalamic mRNA expressions following food deprivation. MCH and GnRH3 cDNAs are maternally deposited into cod eggs, while MCH has variable expression throughout early development. GnRH2 and GnRH3 mRNAs "turn-on" during mid-segmentation once the brain is fully developed. For both MCH and GnRH, highest expression appears during the exogenous feeding stages, perhaps supporting their functions as appetite regulators during early development. MCH and GnRH transcripts are found in brain regions related to appetite regulation (telencephalon/preoptic area, optic tectum/thalamus, hypothalamus), as well as the pituitary gland and the stomach, suggesting a peripheral function in food intake regulation. Atlantic cod MCH mRNA is upregulated during fasting, while GnRH2 and GnRH3 transcripts do not appear to be influenced by food deprivation. In conclusion, MCH might be involved in stimulating food intake in juvenile Atlantic cod, while GnRHs may play a more significant role in appetite regulation during early development. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Estimation of Several Turbulent Fluctuation Quantities Using an Approximate Pulsatile Flow Model

    Energy Technology Data Exchange (ETDEWEB)

    Dechant, Lawrence J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-12-01

    Turbulent fluctuation behavior is approximately modeled using a pulsatile flow model analogy.. This model follows as an extension to the turbulent laminar sublayer model developed by Sternberg (1962) to be valid for a fully turbulent flow domain. Here unsteady turbulent behavior is modeled via a sinusoidal pulsatile approach. While the individual modes of the turbulent flow fluctuation behavior are rather crudely modeled, approximate temporal integration yields plausible estimates for Root Mean Square (RMS) velocity fluctuations. RMS pressure fluctuations and spectra are of particular interest and are estimated via the pressure Poisson expression. Both RMS and Power Spectral Density (PSD), i.e. spectra are developed. Comparison with available measurements suggests reasonable agreement. An additional fluctuating quantity, i.e. RMS wall shear fluctuation is also estimated, yielding reasonable agreement with measurement.

  11. Simulation of a pulsatile non-Newtonian flow past a stenosed 2D artery with atherosclerosis.

    Science.gov (United States)

    Tian, Fang-Bao; Zhu, Luoding; Fok, Pak-Wing; Lu, Xi-Yun

    2013-09-01

    Atherosclerotic plaque can cause severe stenosis in the artery lumen. Blood flow through a substantially narrowed artery may have different flow characteristics and produce different forces acting on the plaque surface and artery wall. The disturbed flow and force fields in the lumen may have serious implications on vascular endothelial cells, smooth muscle cells, and circulating blood cells. In this work a simplified model is used to simulate a pulsatile non-Newtonian blood flow past a stenosed artery caused by atherosclerotic plaques of different severity. The focus is on a systematic parameter study of the effects of plaque size/geometry, flow Reynolds number, shear-rate dependent viscosity and flow pulsatility on the fluid wall shear stress and its gradient, fluid wall normal stress, and flow shear rate. The computational results obtained from this idealized model may shed light on the flow and force characteristics of more realistic blood flow through an atherosclerotic vessel. Copyright © 2013. Published by Elsevier Ltd.

  12. Non-invasive electromagnetic measurement of the peripheral pulsatile blood flow: experimental study and clinical applications.

    Science.gov (United States)

    Boccalon, H J; Candelon, B J; Doll, H G; Puel, P F; Enjalbert, A P

    1978-01-01

    The non-invasive electromagnetic blood flowmeter described in this paper allows us to measure pulsatile flow through a limb. The limb is placed in a magnetic field and the blood flow rate induces electromagnetic forces which are detected at the skin surface with ECG electrodes (Faraday's law). A special computer technique is necessary to isolate the signal from artefacts (local ECG, BCG, EMG). In vitro calibration is performed using a circulatory model and in vivo using mongrel dogs. Its validity is assessed by comparing the results with the responses obtained from the invasive electromagnetic flowmeter. Sources of error in the measurement such as blood composition (Na+, K+), haematocrit (45% to 29%), and venous flow are reported here. The results indicate that the method is reliable, easy to utilise and offers a unique non-invasive way of measuring true pulsatile blood flow rate in humans. Various clinical applications are discussed for possible use of the device.

  13. Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support: a retrospective multicentre study.

    Science.gov (United States)

    Iliodromiti, Stamatina; Blockeel, Christophe; Tremellen, Kelton P; Fleming, Richard; Tournaye, Herman; Humaidan, Peter; Nelson, Scott M

    2013-09-01

    Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)? GnRH agonist trigger combined with 1500 IU hCG at the time of oocyte retrieval and subsequent estradiol and progesterone replacement in OHSS high-risk patients can facilitate fresh embryo transfer with high clinical pregnancy rates and a low risk of severe OHSS. Conventional luteal support packages are inadequate to facilitate a fresh transfer after a GnRH agonist trigger. A low dose of hCG (1500 IU) after oocyte aspiration can be used to replace the actions of early luteal LH to sustain implantation and the function of the early corpus luteum, although the level of risk of severe OHSS with this strategy is unclear. This international multicentre retrospective case study, including 275 women at high risk of OHSS, was undertaken during the period January 2011-December 2012. Women were identified as at high risk of OHSS, based on IVF response, ovarian reserve characteristics and previous history of having had treatment, in three clinical IVF centres in UK, Belgium and Australia. All three centres used a GnRH agonist trigger followed by one bolus of 1500 IU hCG 1h after oocyte retrieval. Moreover, the luteal phase was supported with daily vaginal progesterone and twice daily estradiol valerate. A total of 275 autologous cycles with fresh transfer were undertaken in a cohort of high-risk women as defined by baseline characteristics [median (interquartile range)]: age 31.6 (29-35) years, antral follicle count median 25 (18-34) and anti-Müllerian hormone median 49.1 pmol/l (35.2-69.3). At the end of stimulation, the peak estradiol median of 12 000 pmol/l (9400-15 914) and the mean oocyte yield of 17.8 ± 8.4 confirmed a high response. The overall clinical pregnancy rate was 41.8% per cycle started, with only two cases of severe OHSS reported (0.72%). No

  14. Increased pulsatile intracranial pressure in patients with symptomatic pineal cysts and magnetic resonance imaging biomarkers indicative of central venous hypertension.

    Science.gov (United States)

    Eide, Per Kristian; Ringstad, Geir

    2016-08-15

    In symptomatic individuals with non-hydrocephalic pineal cysts (PCs), it remains controversial what causes the symptoms. Based on magnetic resonance imaging (MRI) biomarkers, we proposed that PC-associated crowding of the pineal recess may cause central venous hypertension. The aim of this study was to compare pulsatile and static ICP in patients with PCs and chronic daily headache (CDH), and compare ICP data in PC patients with the previously identified MRI biomarkers. All patients assessed with over-night ICP monitoring for PCs or CDH who had been ruled out for idiopathic intracranial hypertension without papilledema (IIHWOP) were retrieved from the database. The symptoms as well as the pulsatile and static ICP scores were compared between the PC and CDH patients, and ICP scores were compared with the MRI biomarkers indicative of central venous hypertension. The pulsatile ICP was significantly increased in the symptomatic patients with non-hydrocephalic PCs as compared to the CDH patients. Pulsatile ICP was significantly increased in the individuals with PC-grades 3-4, who had MRI biomarkers indicative of central venous hypertension. The tectum-splenium-cyst ratio correlated positively with pulsatile ICP and an index of thalamic edema. Pulsatile ICP is increased in symptomatic patients with PCs and imaging evidence of central venous hypertension, supporting the hypothesis that PC-induced crowding of the pineal recess and venous obstruction may cause a central venous hypertension syndrome. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Protective Role of GnRH Antagonist on Chemotherapy-induced Spermatogenesis Disorder: A Morphological Study

    Directory of Open Access Journals (Sweden)

    Daryosh Mohammadnejad

    2013-08-01

    Full Text Available Purpose: Anti cancer drugs is one of the most important chemotherapeutic factors which can influence spermatogenesis process and germinal epithelium. Since dividing cells are mainly affected by anticancer drugs, the aim of the present study is to investigate thepreventive effect of GnRH antagonist on spermatogenic defect produced by anticancer drugs. Methods: In the present study thirty adult male mice aging 6-8 weeks were divided into 3 groups as: Control, Experimental 1 and Experimental 2. Experimental 1 group received Cisplatin for 5 days as 2.5 mg/kg intraperitoneally and Experimental 2group received 0.25 mg/kg cetrorelix (GnRH antagonist one week before cisplatin treatment and continued for 3 weeks. The mice in all groups were sacrificed 35 days after the last injection and testis specimens were fixed in boueins, formaldehyde fixativeand 2.5% Glutaraldehide then prepared for light and electron microscopic examination. Results: Light microscopy (LM study showed that the number of spermatogonial cells, thickness of germinal epithelium, was decreased in Experimental 1group. Electronmicroscopy revealed that in this group several intercellular spaces appeared between spermatogenic cells and secretory granules in interstitial cells was increased. There were several vacuolated mitochondria and destroyed organelles in spermatogonial cells but inExperimental 2 group condition was similar to control group. Conclusion: These results indicate that the cetrorelix administration before cancer treatment may protect germinal epithelium against side effects of cisplatin.

  16. Development of a Ga-68 labeled triptorelin analog for GnRH receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zoghi, Masoumeh; Niazi, Ali [Islamic Azad Univ., Arak (Iran, Islamic Republic of). Dept. of Chemistry; Jalilian, Amir R.; Johari-daha, Fariba; Alirezapour, Behrouz [Nuclear Science and Technology Research Institute (NSTRI) (Iran, Islamic Republic of). Radiation Application Research School; Ramezanpour, Sorour [K.N. Toosi Univ. of Technology, Tehran (Iran, Islamic Republic of). Peptide Chemistry Research Center

    2016-08-01

    Optimized total synthesis, radiolabeling and quality control of [{sup 68}Ga]-DOTA-Hyd-TRP as an efficient and possible PET radiotracer for GnRH receptor imaging in various tumors is of great interest. DOTA-Hyd-TRP was synthesized using solid phase peptide synthesis followed by conjugation to DOTA using pSCN-Bn-DOTA. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared using generator-based [{sup 68}Ga]GaCl{sub 3} and DOTA-Hyd-TRP under optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting up to 120 min. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared at optimized conditions in 5-7 min at 95 C followed by separation using C{sub 18} cartridge (radiochemical purity ∼99 ± 0.88% ITLC, > 99% HPLC, specific activity: 300 ± 15 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min as well as significant testicular uptake consistent with reported GnRH receptor mappings. Block test studies by triptorelin pretreatment of the animals prior to tracer administration demonstrated significant specific uptake in receptor rich organs including testes and stomach.

  17. A minimalist model of calcium-voltage coupling in GnRH cells

    Energy Technology Data Exchange (ETDEWEB)

    Rennie, Martin; Chan, Rossanna; Duan Wen; Sneyd, James [Department of Mathematics, University of Auckland, Auckland 1142 (New Zealand); Schneider, David, E-mail: schneide@tandar.cnea.gov.ar [Departamento de Fisica, Comision Nacional de Energia Atomica. Av. del Libertador 8250, 1429 Buenos Aires (Argentina)

    2011-03-01

    We present a minimalist model to describe the interplay between burst firing and calcium dynamics in Gonadotropin-releasing hormone (GnRH) cells. This model attempts to give a qualitative representation of Duan's model [3], and it comprises two FithzHugh-Nagumo (FHN) coupled systems describing the dynamics of the membrane potential and calcium concentration in the GnRH cells. Within the framework of our minimalist model, we find that the calcium subsystem drives burst firing by making the voltage subsystem to undergo a Hopf bifurcation. Specifically, fast relaxation oscillations occur in a specific region of the c-z plane (c being the calcium concentration, and z a calcium-dependent gating variable). Slow calcium oscillations, instead, are carried by the voltage subsystem by successive shifts of the calcium steady state, and have the net effect of an external perturbation. The full comprehension of the phase-plane of the voltage subsystem and the 3-dimensional phase-space of the calcium subsystem ultimately allows us to study the behaviours of the entire model under the change of certain parameters. Those special parameters do not necessarily follow realistic assumptions, but merely intend to mimic some pharmacological tests which have been performed experimentally and also simulated by Duan's model under the corresponding physiological considerations.

  18. The correlation between GnRH stimulation testing and obstetric ultrasonographic parameters in precocious puberty.

    Science.gov (United States)

    Binay, Cigdem; Simsek, Enver; Bal, Cengiz

    2014-11-01

    The aim of this study was to determine reliable cut-off levels of basal gonadotropin and to assess the correlation of obstetric ultrasound parameters with the GnRH stimulation test. The GnRH stimulation test was performed in a cohort of young female patients who presented at our hospital for the evaluation of early signs of puberty. Using receiver operating curves (ROCs), the sensitivity and specificity of basal luteinising hormone (LH), follicle stimulating hormone (FSH), basal and stimulated LH/FSH ratio, oestradiol levels and ultrasonographic parameters were evaluated at each level, and the area under curve (AUC) was measured. One hundred female children were assessed. We found that LH levels, peak LH/FSH ratio, fundal/cervical ratio, uterus length, and ovarian volume were reliable predictors of central precocious puberty (CPP). Cut-off levels of basal LH and the peak LH/FSH ratio had high specificity in our cohort. In addition, obstetric ultrasound parameters represent reliable predictors for the diagnosis of CPP.

  19. The control of reproduction in finfish species through GnRH treatments

    Directory of Open Access Journals (Sweden)

    Simona Rainis

    2010-01-01

    Full Text Available Fish in captivity can show some dysfunctions, at different levels, in the physiological processes of reproduction, due to  the lack of synthesis or release of gonadotropins (GtHs by hypophysis. As a consequence, a worsening of quality and  quantity of spawned gametes, or a lack of egg and sperm spawning, can be observed. The farmers can act on fish repro-  ductive cycle manipulating the environmental parameters of rearing, the diet, the genetics or using GnRH treatments.  Nowadays, they are used mainly GnRH, synthesized in laboratory as analogues. These releasing factors, naturally pro-  duced by hypothalamus, let to overcome the technological and biological limits of the “traditional” hormonal treatments  with hCG, being more effective, cheaper and easily available on market. This article makes a historical survey of the con-  ditioning treatments for fish reproduction and also considers the future perspectives of these treatments, examining the  topics that research will have to focus, in order to make these treatments common worldwide, in any hatchery and for  each farmed  species of finfish. 

  20. [Design and construction of pulsatile-flow-cultivation system for the tissue engineering heart valve].

    Science.gov (United States)

    Feng, Bin; Liu, Yinglong; Yan, Mingquan; He, Guojian; Yu, Cuntao; Xie, Ning

    2007-06-01

    A plane, three-dimensional chamber of pulsatile-flow-cultivation and the liquid store chamber connected by medical silica gel tube were designed and constructed by ourselves according to the design principle. The rotator pump of cardiopulmonary bypass unit was acted as the power source. The mixed gas containing 5% CO2 and 95% air was supplied through the ventilation orifice of the liquid store chamber. The temperature of these components was stabilized by thermostatic waterbath. The test of biomechanics and biological compatibility for the system was carried out by cultures experiment during two weeks. The results of the experiment showed that there was no leak in the pulsatile-flow-cultivation components in which the concentration of CO2 was controlled about 5%+1%, the temperature at 37 +/- 1 degree C, and the value of pH between 6.8 and 7.5. The flow rate of the system could be adjusted exactly between 0.125 L/min and 6.0 L/min. The endothelial cells on the viable homograft valve increased about 10 times after being cultured for 2 weeks. The cultures of cell and mould taken from the leaf and Dacron cloth of homograft valve were reported to be negative. The results of the experiment demonstrated that there was satisfactory homeostasis of these components in effective modeling pulsatile-flow-field for the implantation cells cultured, proliferated, and remodeled under the condition inferior or superior to physiological level in vitro. The system can meet the need for study of pulsatile-flow-cultivation and tissue engineering heart valve constructed in vitro.

  1. White matter hyperintensities in migraine: Clinical significance and central pulsatile hemodynamic correlates.

    Science.gov (United States)

    Cheng, Chun-Yu; Cheng, Hao-Min; Chen, Shih-Pin; Chung, Chih-Ping; Lin, Yung-Yang; Hu, Han-Hwa; Chen, Chen-Huan; Wang, Shuu-Jiun

    2017-01-01

    Background The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities in migraine patients has not been clarified. Methods Sixty patients with migraine (20-50 years old; women, 68%) without overt vascular risk factors and 30 demographically-matched healthy controls were recruited prospectively. Cerebral white matter hyperintensities volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure, carotid-femoral pulse wave velocity, and carotid augmentation index were measured by applanation tonometry. Carotid pulsatility index was derived from Doppler ultrasound carotid artery flow analysis. Results Compared to the controls, the migraine patients had higher white matter hyperintensities frequency (odds ratio, 2.75; p = 0.04) and greater mean white matter hyperintensities volume (0.174 vs. 0.049, cm3, p = 0.04). Multivariable regression analysis showed that white matter hyperintensities volume in migraine patients was positively associated with central systolic blood pressure ( p = 0.04) and carotid-femoral pulse wave velocity ( p matter hyperintensities formation was greater for the lower-carotid pulsatility index subgroup of migraine patients. White matter hyperintensities volume in migraine patients increased with decreasing carotid pulsatility index and with increasing central systolic blood pressure or carotid-femoral pulse wave velocity. Conclusions White matter hyperintensities are more common in patients with migraine than in healthy controls. Increased aortic stiffness or central systolic blood pressure in the presence of low intracranial artery resistance may predispose patients with migraine to white matter hyperintensities formation.

  2. Feasibility Study of Ex Ovo Chick Chorioallantoic Artery Model for Investigating Pulsatile Variation of Arterial Geometry.

    Directory of Open Access Journals (Sweden)

    Kweon-Ho Nam

    Full Text Available Despite considerable research efforts on the relationship between arterial geometry and cardiovascular pathology, information is lacking on the pulsatile geometrical variation caused by arterial distensibility and cardiomotility because of the lack of suitable in vivo experimental models and the methodological difficulties in examining the arterial dynamics. We aimed to investigate the feasibility of using a chick embryo system as an experimental model for basic research on the pulsatile variation of arterial geometry. Optical microscope video images of various arterial shapes in chick chorioallantoic circulation were recorded from different locations and different embryo samples. The high optical transparency of the chorioallantoic membrane (CAM allowed clear observation of tiny vessels and their movements. Systolic and diastolic changes in arterial geometry were visualized by detecting the wall boundaries from binary images. Several to hundreds of microns of wall displacement variations were recognized during a pulsatile cycle. The spatial maps of the wall motion harmonics and magnitude ratio of harmonic components were obtained by analyzing the temporal brightness variation at each pixel in sequential grayscale images using spectral analysis techniques. The local variations in the spectral characteristics of the arterial wall motion were reflected well in the analysis results. In addition, mapping the phase angle of the fundamental frequency identified the regional variations in the wall motion directivity and phase shift. Regional variations in wall motion phase angle and fundamental-to-second harmonic ratio were remarkable near the bifurcation area. In summary, wall motion in various arterial geometry including straight, curved and bifurcated shapes was well observed in the CAM artery model, and their local and cyclic variations could be characterized by Fourier and wavelet transforms of the acquired video images. The CAM artery model with

  3. Impact of Distinct Oxygenators on Pulsatile Energy Indicators in an Adult Cardiopulmonary Bypass Model.

    Science.gov (United States)

    Griep, Lonneke M; van Barneveld, Laurentius J M; Simons, Antoine P; Boer, Christa; Weerwind, Patrick W

    2017-02-01

    The quantification of pulse energy during cardiopulmonary bypass (CPB) post-oxygenator is required prior to the evaluation of the possible beneficial effects of pulsatile flow on patient outcome. We therefore, evaluated the impact of three distinctive oxygenators on the energy indicators energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) in an adult CPB model under both pulsatile and laminar flow conditions. The pre- and post-oxygenator pressure and flow were measured at room temperature using a 40% glycerin-water mixture at flow rates of 1, 2, 3, 4, 5, and 6 L/min. The pulse settings at frequencies of 40, 50, 60, 70, and 80 beats per minute were according to the internal algorithm of the Sorin CP5 centrifugal pump. The EEP is equal to the mean pressure, hence no SHE is present under laminar flow conditions. The Quadrox-i Adult oxygenator was associated with the highest preservation of pulsatile energy irrespective of flow rates. The low pressure drop-high compliant Quadrox-i Adult oxygenator shows the best SHE performance at flow rates of 5 and 6 L/min, while the intermediate pressure drop-low compliant Fusion oxygenator and the high pressure drop-low compliant Inspire 8F oxygenator behave optimally at flow rates of 5 L/min and up to 4 L/min, respectively. In conclusion, our findings contributed to studies focusing on SHE values post-oxygenator as well as post-cannula in clinical practice. In addition, our findings may give guidance to the clinical perfusionist for oxygenator selection prior to pulsatile CPB based on the calculated flow rate for the individual patient. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  4. Validation of a stereo camera system to quantify brain deformation due to breathing and pulsatility.

    Science.gov (United States)

    Faria, Carlos; Sadowsky, Ofri; Bicho, Estela; Ferrigno, Giancarlo; Joskowicz, Leo; Shoham, Moshe; Vivanti, Refael; De Momi, Elena

    2014-11-01

    A new stereo vision system is presented to quantify brain shift and pulsatility in open-skull neurosurgeries. The system is endowed with hardware and software synchronous image acquisition with timestamp embedding in the captured images, a brain surface oriented feature detection, and a tracking subroutine robust to occlusions and outliers. A validation experiment for the stereo vision system was conducted against a gold-standard optical tracking system, Optotrak CERTUS. A static and dynamic analysis of the stereo camera tracking error was performed tracking a customized object in different positions, orientations, linear, and angular speeds. The system is able to detect an immobile object position and orientation with a maximum error of 0.5 mm and 1.6° in all depth of field, and tracking a moving object until 3 mm/s with a median error of 0.5 mm. Three stereo video acquisitions were recorded from a patient, immediately after the craniotomy. The cortical pulsatile motion was captured and is represented in the time and frequency domain. The amplitude of motion of the cloud of features' center of mass was inferior to 0.8 mm. Three distinct peaks are identified in the fast Fourier transform analysis related to the sympathovagal balance, breathing, and blood pressure with 0.03-0.05, 0.2, and 1 Hz, respectively. The stereo vision system presented is a precise and robust system to measure brain shift and pulsatility with an accuracy superior to other reported systems.

  5. Generating pulsatility by pump speed modulation with continuous-flow total artificial heart in awake calves.

    Science.gov (United States)

    Fukamachi, Kiyotaka; Karimov, Jamshid H; Sunagawa, Gengo; Horvath, David J; Byram, Nicole; Kuban, Barry D; Dessoffy, Raymond; Sale, Shiva; Golding, Leonard A R; Moazami, Nader

    2017-12-01

    The purpose of this study was to evaluate the effects of sinusoidal pump speed modulation of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) on hemodynamics and pump flow in an awake chronic calf model. The sinusoidal pump speed modulations, performed on the day of elective sacrifice, were set at ±15 and ± 25% of mean pump speed at 80 bpm in four awake calves with a CFTAH. The systemic and pulmonary arterial pulse pressures increased to 12.0 and 12.3 mmHg (±15% modulation) and to 15.9 and 15.7 mmHg (±25% modulation), respectively. The pulsatility index and surplus hemodynamic energy significantly increased, respectively, to 1.05 and 1346 ergs/cm at ±15% speed modulation and to 1.51 and 3381 ergs/cm at ±25% speed modulation. This study showed that it is feasible to generate pressure pulsatility with pump speed modulation; the platform is suitable for evaluating the physiologic impact of pulsatility and allows determination of the best speed modulations in terms of magnitude, frequency, and profiles.

  6. Vortex propagation around a wall-mounted obstacle in pulsatile flow

    Science.gov (United States)

    Carr, Ian A.; Plesniak, Michael W.

    2015-11-01

    Wall-mounted obstacles are prevalent in nature and engineering applications. Physiological flows observed in human vocal fold pathologies, such as polyps, can be modeled by flow over a wall-mounted protuberance. Despite their prevalence, studies of wall-mounted obstacles have been restricted to steady (constant velocity) freestream flow. In biological and geophysical applications, pulsatile flow is much more common, yet effects of pulsatility on the wake of a wall-mounted obstacle remain to be extensively studied. This study aims to characterize the complex physics produced in this unsteady, separated flow. Experiments were performed in a low-speed wind tunnel with a set of rotating vanes, which produce the pulsatile inflow waveform. Instantaneous and phase-averaged particle image velocimetry (PIV) results acquired around a hemispherical obstacle are presented and compared. A mechanism based on self-induced vortex propagation, analogous to that in vortex rings, is proposed to explain the observed dynamics of coherent structures. Predictions of the propagation velocity based on analytical expressions for vortex rings in a viscous fluid are compared to the experimentally measured propagation velocity. Effects of the unsteady boundary layer on the observed physics are explored. This material is based in part upon work supported by the National Science Foundation under Grant Number CBET-1236351, and GW Center for Biomimetics and Bioinspired Engineering (COBRE).

  7. Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol

    Directory of Open Access Journals (Sweden)

    Swati C. Jagdale

    2013-01-01

    Full Text Available The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT F13 at level 0 (55 mg for Polyox WSR205 and level +1 (65 mg for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P<0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

  8. Simulations of pulsatile suspension flow through bileaflet mechanical heart valves to quantify platelet damage

    Science.gov (United States)

    Yun, Brian; Aidun, Cyrus; Yoganathan, Ajit

    2012-11-01

    Studies have shown that high shear stress and long exposure times on platelets have a strong impact on thromboembolic complications in bileaflet mechanical heart valves (BMHVs). This numerical study quantifies the platelet damage incurred in pulsatile flow through various BMHV designs. The lattice-Boltzmann method with external boundary force (LBM-EBF) was implemented to simulate pulsatile flow and capture the dynamics and surface shear stresses of modeled platelets with realistic geometry. The platelets are released in key regions of interest in the geometry as well as at various times of the cardiac cycle. The platelet damage is quantified using a linear shear stress-exposure time blood damage index (BDI) model. The multiscale computational method used to quantitatively measure the BDI during the pulsatile flow has been validated as being able to accurately capture bulk BMHV fluid flow and for accurately quantifying platelet damage in BMHV flows. These simulations will further knowledge of the geometric features and cardiac cycle times that most affect platelet damage. This study will ultimately lead to optimization of BMHV design in order to minimize thromboembolic complications.

  9. Molecular analysis of the koala reproductive hormones and their receptors: gonadotrophin-releasing hormone (GnRH), follicle-stimulating hormone β and luteinising hormone β with localisation of GnRH.

    Science.gov (United States)

    Busby, E R; Soeta, S; Sherwood, N M; Johnston, S D

    2014-12-01

    During evolution, reproductive hormones and their receptors in the brain-pituitary-gonadal axis have been altered by genetic mechanisms. To understand how the neuroendocrine control of reproduction evolved in mammals, it is important to examine marsupials, the closest group to placental mammals. We hypothesised that at least some of the hormones and receptors found in placental mammals would be present in koala, a marsupial. We examined the expression of koala mRNA for the reproductive molecules. Koala cDNAs were cloned from brain for gonadotrophin-releasing hormones (GnRH1 and GnRH2) or from pituitary for GnRH receptors, types I and II, follicle-stimulating hormone (FSH)β and luteinising hormone (LH)β, and from gonads for FSH and LH receptors. Deduced proteins were compared by sequence alignment and phylogenetic analysis with those of other vertebrates. In conclusion, the koala expressed mRNA for these eight putative reproductive molecules, whereas at least one of these molecules is missing in some species in the amniote lineage, including humans. In addition, GnRH1 and 2 are shown by immunohistochemistry to be expressed as proteins in the brain. © 2014 British Society for Neuroendocrinology.

  10. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization

    NARCIS (Netherlands)

    B.C.J.M. Fauser (Bart); D. de Jong (Danielle); F. Olivennes; H. Wramsby; C. Tay; J. Itskovitz-Eldor; H.G. van Hooren

    2002-01-01

    textabstractIn a randomized multicenter study, the efficacies of two different GnRH agonists were compared with that of hCG for triggering final stages of oocyte maturation after ovarian hyperstimulation for in vitro fertilization. Ovarian stimulation was conducted by recombinant

  11. Impact of Pulsatility and Flow Rates on Hemodynamic Energy Transmission in an Adult Extracorporeal Life Support System.

    Science.gov (United States)

    Wolfe, Rachel; Strother, Ashton; Wang, Shigang; Kunselman, Allen R; Ündar, Akif

    2015-07-01

    This study investigated the total hemodynamic energy (THE) and surplus hemodynamic energy transmission (SHE) of a novel adult extracorporeal life support (ECLS) system with nonpulsatile and pulsatile settings and varying pulsatility to define the most effective setting for this circuit. The circuit consisted of an i-cor diagonal pump (Xenios AG, Heilbronn, Germany), an XLung membrane oxygenator (Xenios AG), an 18 Fr Medos femoral arterial cannula (Xenios AG), a 23/25 Fr Estech RAP femoral venous cannula (San Ramon, CA, USA), 3/8 in ID × 140 cm arterial tubing, and 3/8 in ID × 160 cm venous tubing. Priming was done with lactated Ringer's solution and packed red blood cells (HCT 36%). The trials were conducted at flow rates 1-4 L/min (1 L/min increments) under nonpulsatile and pulsatile mode, with differential speed values 1000-4000 rpm (1000 rpm increments) at 36°. The pseudo patient's mean arterial pressure was kept at 100 mm Hg using a Hoffman clamp during all trials. Real-time flow and pressure data were collected using a custom-based data acquisition system. Mean pressures across the circuit increased with increasing flow rates, but increased insignificantly with increasing differential speed values. Mean pressure did not change significantly between pulsatile and nonpulsatile modes. Pulsatile flow created more THE than nonpulsatile flow at the preoxygenator site (P flow rates. No SHE was created with nonpulsatile flow, but SHE was created with pulsatile flow, and increased with increasing differential speed values. At lower flow rates (1-2 L/min), the arterial cannula contributed the most to SHE loss, but at higher flow rates the arterial tubing created the most SHE loss. The circuit pressure drop values across all flow rates were 33.1-246.5 mm Hg, and were slightly higher under pulsatile mode than nonpulsatile mode. The i-cor diagonal pump creates satisfactory pulsatile and nonpulsatile flows, and can easily change the

  12. Non-dimensional physics of pulsatile cardiovascular networks and energy efficiency.

    Science.gov (United States)

    Yigit, Berk; Pekkan, Kerem

    2016-01-01

    In Nature, there exist a variety of cardiovascular circulation networks in which the energetic ventricular load has both steady and pulsatile components. Steady load is related to the mean cardiac output (CO) and the haemodynamic resistance of the peripheral vascular system. On the other hand, the pulsatile load is determined by the simultaneous pressure and flow waveforms at the ventricular outlet, which in turn are governed through arterial wave dynamics (transmission) and pulse decay characteristics (windkessel effect). Both the steady and pulsatile contributions of the haemodynamic power load are critical for characterizing/comparing disease states and for predicting the performance of cardiovascular devices. However, haemodynamic performance parameters vary significantly from subject to subject because of body size, heart rate and subject-specific CO. Therefore, a 'normalized' energy dissipation index, as a function of the 'non-dimensional' physical parameters that govern the circulation networks, is needed for comparative/integrative biological studies and clinical decision-making. In this paper, a complete network-independent non-dimensional formulation that incorporates pulsatile flow regimes is developed. Mechanical design variables of cardiovascular flow systems are identified and the Buckingham Pi theorem is formally applied to obtain the corresponding non-dimensional scaling parameter sets. Two scaling approaches are considered to address both the lumped parameter networks and the distributed circulation components. The validity of these non-dimensional number sets is tested extensively through the existing empirical allometric scaling laws of circulation systems. Additional validation studies are performed using a parametric numerical arterial model that represents the transmission and windkessel characteristics, which are adjusted to represent different body sizes and non-dimensional haemodynamic states. Simulations demonstrate that the proposed non

  13. Hysteroscopic myomectomy outcomes after 3-month treatment with either Ulipristal Acetate or GnRH analogues: a retrospective comparative study.

    Science.gov (United States)

    Sancho, Javier Monleón; Delgado, Verónica Serrano de la Cruz; Valero, Maria José Nuñez; Soteras, Marta Gurrea; Amate, Vicente Payá; Carrascosa, Antonio Abad

    2016-03-01

    Ulipristal Acetate (UPA) modifies the endometrium, as well as fibroids, and therefore it might make hysteroscopic surgery more difficult. To confirm that pre-treatment with UPA is as safe and effective an option as pre-treatment with GnRH analogues, considered the gold standard. We present the first series of 26 hysteroscopic myomectomies after 3 months treatment with UPA and we compare the results with a series of 24 cases pretreated with GnRH analogues. This was a retrospective cohort study between July 2013 and May 2015. We analyszed patients with submucous myomas >2.5 in diameter. Hysteroscopic myomectomy was performed after 3 months of treatment with either UPA (5mg daily) or the GnRH agonist (3.75mg/month). Both groups were similar in age, myoma initial size and classification. There were no significant differences between UPA and GnRHa treated groups in terms of percentage of myomas resected (93% vs 98%), duration of surgery (38 vs 37min), fluid deficit (200 vs 350ml) and complications. In the surgeon's subjective opinion, UPA treatment was associated with an easier resection. Based on our experience, previous treatment with UPA does not difficult Hhysteroscopic myomectomy. Endometrial changes have no impact on surgery. Safety and feasibility are comparable to hysteroscopic myomectomies with previous treatment with GnRH analogues. This allows us to take advantage of the reduction in size of fibroids before surgery with less side effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Active immunization against GnRH in ovine (Ovis aries: testicular morphometry, histopathology and endocrine responses in prepubertal ram lambs

    Directory of Open Access Journals (Sweden)

    Gutierrez-Reinoso MA

    2017-08-01

    Full Text Available The main objective of the present research was to assess the effects of an active immunization against GnRH on male reproductive function as an alternative to surgical sterilization evaluating testicular morphometry, histopathological alterations and plasma gonadotropin levels in prepubertal ram lambs. Dorper ram lambs (age= 2 months; control group, n= 5; treatment group, n=15 were immunised by using an anti-GnRH vaccine (two administrations spaced 15d developed by linking a GnRH homologous molecule to tetanus toxoid (clostridial toxoid with aluminum hydroxide as coadjuvant. To determine the effectiveness of the vaccination protocol, testicular morphometry was evaluated (length, width, mean volume and total volume together with histopathological alterations in testicular tissue samples (seminiferous tubule diameters, spermatogonia per testis and sperm presence and endocrine responses (ELISA from blood samples (FSH, LH, testosterone and cortisol plasma levels. Morphometric parameters (testicular length, width and volume were significantly reduced in vaccinated animals with respect to the control group (p0.05. In conclusion, prepubertal active immunization against GnRH led to marked differences on testes morphometry and activity in ovine species, however, it did not affect endocrine levels nor spermatogenesis in all individuals studied showing a partial vaccination effect in some of them. Thus, taking into account the heterogeneous dysfunctional responses obtained, different vaccination assays and strategies should be tested before active immunization against GnRH is considered as a viable alternative to conventional surgical sterilization.

  15. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist

    NARCIS (Netherlands)

    Oostdijk, W; Rikken, B; Schreuder, S; Otten, Barto; Odink, R; Rouwe, C; Jansen, M; Gerver, WJ; Waelkens, J; Drop, S

    1996-01-01

    Objective-To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. Patients-31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were

  16. Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment

    DEFF Research Database (Denmark)

    Juul, A; Müller, J; Skakkebaek, N E

    1997-01-01

    antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with GnRH...

  17. FSH inhibits the augmentation by oestradiol of the pituitary responsiveness to GnRH in the female rat

    NARCIS (Netherlands)

    Schuiling, GA; Valkhof, N; Koiter, TR

    The effect of follicle stimulating hormone (FSH) treatment on the pituitary response to gonadotrophin-releasing hormone (GnRH) was studied in rats in various reproductive conditions. A 3-day treatment of cycling rats with FSH (Metrodin(R); 10 IU/injection) lowered the spontaneous pre-ovulatory

  18. Use of GnRH to induce an accessory corpus luteum in buffaloes fixed time artificially inseminated

    Directory of Open Access Journals (Sweden)

    P.S. Baruselli

    2010-02-01

    Full Text Available The objective of this study was to induce an accessory corpus luteum (CL in buffaloes fixed time artificially inseminated. Two hundred and forty buffaloes received the treatment sequence GnRH/PGF2α/GnRH after which were inseminated artificially. Six days after the insemination, the animals were divided in two groups (G1 = Control and G2 = GnRH and received 0 μg or 25 μg of GnRH to induce an accessory CL. After twenty four days (D40, pregnancy diagnosis was performed by ultrasonography and 79 buffalo (G1, n = 39; G2, n = 40 were randomly selected to verify the ovary status by ultrasound. Fifty three pregnant buffaloes (G1, n = 32; G2, n = 21 were followed to verify the birth rate. Data were analyzed by Chi-square test. The conception rate, the accessory CL rate and the birth rate were higher in G2 than in G1 (P<0.05. The use of GnRH to induce an accessory CL in buffaloes increased the conception and birth rates. Thus, the increase of the cost of Ovsynch protocol with the thirty dose of GnRH is rewarded by the increment on conception and birth rates and reduction of days open.

  19. Active immunization with recombinant GnRH fusion protein in boars reduces both testicular development and mRNA expression levels of GnRH receptor in pituitary.

    Science.gov (United States)

    Fang, Fugui; Li, Haidong; Liu, Ya; Zhang, Yunhai; Tao, Yong; Li, Yunsheng; Cao, Hongguo; Wang, Suolu; Wang, Lin; Zhang, Xiaorong

    2010-06-01

    Immunization using recombinant maltose binding protein-gonadotropin releasing hormone (MBP-GnRH6) altered both testicular development and transcription of the pituitary GnRH receptor (GnRHR) gene in boars. Scrotal measurement and blood samples were taken at 4-week interval after immunization at 9 weeks of age. The concentrations of testosterone and anti-GnRH antibodies in serum were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The results showed that active immunization with MBP-GnRH6 increased the serum concentration of anti-GnRH antibodies (Pimmunized animals as compared with MBP immunized boars. MBP-GnRH6 immunized pigs exhibited mounting behavior 4 weeks later than MBP immunized boars. No mature spermatozoa were observed from MBP-GnRH6 immunized animals. By real-time quantitative PCR analysis, the amount of GnRHR mRNA in the pituitary tissue was found to be significantly lower in MBP-GnRH6 immunized animals than in controls (P<0.05). These data demonstrate that recombinant MBP-GnRH6 was effective in immunological castration in boars. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  20. Regulation of luteinizing hormone (LH) subunit biosynthesis in cultured male anterior pituitary cells: effects of GnRH and testosterone

    Energy Technology Data Exchange (ETDEWEB)

    Krummen, L.A.

    1988-01-01

    The purpose of this study was to evaluate the direct effects of testosterone (T) on LH subunit apoprotein synthesis, glycosylation and release by the male pituitary. Cells from 1 wk castrate rats were cultured for 48 h in steroid-free medium followed by 48h in media /+-/10nM T. The cells were then incubated for 2, 4, 6, 8, or 12h in media containing (/sup 35/S)-methionine (/sup 35/S-Met) or (/sup 3/H)-glucosamine (/sup 3/H-Gln), /+-/1nM GnRH (exp 1) or in media containing precursors /+-/ 10nM T and/or 1nM GnRH (exp 2). Radiolabeled precursor incorporation into LH subunits was determined by immunoprecipitation followed by SDS-PAGE. In experiment 1, precursor incorporation into total protein (TP) and LH subunits increased linearly with time for at least 8h. GnRH did not effect precursor incorporation in to TP or /sup 35/S-Met labeling of LH subunits, but stimulated a linear, time-dependent accumulation of /sup 3/H-Gln into total LH subunits and the release of RIA-LH and radiolabeled subunits into media. Based on these results, the effects of T on LH subunit biosynthesis were studied during an 8h incubation. In experiment 2, GnRH enhanced the total /sup 3/H-Gln incorporation (but not /sup 35/S-Met incorporation) into both LH subunits. GnRH stimulated the release of /sup 35/S-Met LH..cap alpha.. and /sup 3/H-Gln LH subunits into media and increased the relative glycosylation of secreted LH subunits without altering the relative glycosylation of intracellular LH subunits. T inhibited RIA-LH release and incorporation of both precursors into total and secreted LH subunits (/+-/GnRH). However, only the relative glycosylation of secreted LH..cap alpha.. was reduced by T (/+-/GnRh).

  1. Effect of GnRH and hCG on progesterone concentration and ovarian and luteal blood flow in diestrous mares.

    Science.gov (United States)

    Brito, L F C; Baldrighi, J M; Wolf, C A; Ginther, O J

    2017-01-01

    The objective of the present study was to investigate the effect of reproductive hormones (GnRH, hCG, LH and progesterone) on the regulation of corpus luteum (CL) and ovarian blood flow. Diestrous mares received a single treatment of saline, 100μg gonadorelin (GnRH), or 1500IU hCG 10days after ovulation. Plasma LH and progesterone concentrations, resistance index (RI) for ovarian artery blood-flow, and percentage of corpus luteum (CL) with color-Doppler signals of blood flow were determined immediately before treatment (hour 0) and at hours 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 6. In the GnRH group, LH increased (PhCG groups. Progesterone concentration was not different among groups. In the GnRH group, RI tended (PhCG group, two transient RI decreases (PhCG group. The similarity among groups in progesterone concentration indicated that changes in progesterone were not involved in the GnRH and hCG stimulation of ovarian vascular perfusion. Effects of treatment might have been mediated through LH; however, since hCG biological activity is primarily LH-like, the differences in timing and degree of ovarian and luteal blood flow changes after GnRH or hCG administration in the present study suggest that GnRH might have a direct effect on ovarian blood vessels and vascular control. Copyright © 2016. Published by Elsevier B.V.

  2. The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics: a time-lapse study.

    Science.gov (United States)

    Muñoz, Manuel; Cruz, María; Humaidan, Peter; Garrido, Nicolás; Pérez-Cano, Inmaculada; Meseguer, Marcos

    2013-06-01

    To explore if the GnRH analogue used for controlled ovarian stimulation (COS) and the ovulation triggering factor (GnRH agonist + hCG triggering versus GnRH antagonist + GnRH agonist triggering) affect embryo development and kinetics. In a retrospective cohort study in the Instituto Valenciano de Infertilidad (IVI) Alicante and the Instituto Universitario-IVI Valencia, Spain, 2817 embryos deriving from 400 couples undergoing oocyte donation were analysed. After controlled ovarian stimulation and IVF/intracytoplamic sperm injection, the timing of embryonic cleavages was assessed by a video time-lapse system. The results were analysed using Student's t test for comparison of timings (hours) and Chi-squared test for comparison of proportions. A p-value < 0.05 was considered to be statistically significant. Embryos from cycles co-treated with GnRH antagonist + GnRH agonist (n = 2101) cleaved faster than embryos deriving from patients co-treated with GnRH agonist + hCG (n = 716): these differences were significant at the first stages of development but they disappeared as long as the embryo developed. Assessing embryo quality in terms of morphokinetic characteristics, we did not find significant differences between the two groups. By adopting a time-lapse video system, we can suggest that the type of protocol used for controlled ovarian stimulation influences embryo kinetics of development but these variations are not reflected in embryo quality. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells

    Science.gov (United States)

    Terasaka, Tomohiro; Otsuka, Fumio; Tsukamoto, Naoko; Nakamura, Eri; Inagaki, Kenichi; Toma, Kishio; Ogura-Ochi, Kanako; Glidewell-Kenney, Christine; Lawson, Mark A.; Makino, Hirofumi

    2014-01-01

    Reproduction is integrated by interaction of neural and hormonal signals converging on hypothalamic neurons for controlling gonadotropin-releasing hormone (GnRH). Kisspeptin, the peptide product of the kiss1 gene and the endogenous agonist for the GRP54 receptor, plays a key role in the regulation of GnRH secretion. In the present study, we investigated the interaction between kisspeptin, estrogen and BMPs in the regulation of GnRH production by using mouse hypothalamic GT1-7 cells. Treatment with kisspeptin increased GnRH mRNA expression and GnRH protein production in a concentrationdependent manner. The expression levels of kiss1 and GPR54 were not changed by kisspeptin stimulation. Kisspeptin induction of GnRH was suppressed by co-treatment with BMPs, with BMP-4 action being the most potent for suppressing the kisspeptin effect. The expression of kisspeptin receptor, GPR54, was suppressed by BMPs, and this effect was reversed in the presence of kisspeptin. It was also revealed that BMP-induced Smad1/5/8 phosphorylation and Id-1 expression were suppressed and inhibitory Smad6/7 was induced by kisspeptin. In addition, estrogen induced GPR54 expression, while kisspeptin increased the expression levels of ERα and ERβ, suggesting that the actions of estrogen and kisspeptin are mutually enhanced in GT1-7 cells. Moreover, kisspeptin stimulated MAPKs and AKT signaling, and ERK signaling was functionally involved in the kisspeptin-induced GnRH expression. BMP-4 was found to suppress kisspeptin-induced GnRH expression by reducing ERK signaling activity. Collectively, the results indicate that the axis of kisspeptin-induced GnRH production is bi-directionally controlled, being augmented by an interaction between ERα/β and GPR54 signaling and suppressed by BMP-4 action in GT1-7 neuron cells. PMID:23880664

  4. Dynamics of GnRH Neuron Ionotropic GABA and Glutamate Synaptic Receptors Are Unchanged during Estrogen Positive and Negative Feedback in Female Mice.

    Science.gov (United States)

    Liu, Xinhuai; Porteous, Robert; Herbison, Allan E

    2017-01-01

    Inputs from GABAergic and glutamatergic neurons are suspected to play an important role in regulating the activity of the gonadotropin-releasing hormone (GnRH) neurons. The GnRH neurons exhibit marked plasticity to control the ovarian cycle with circulating estradiol concentrations having profound "feedback" effects on their activity. This includes "negative feedback" responsible for suppressing GnRH neuron activity and "positive feedback" that occurs at mid-cycle to activate the GnRH neurons to generate the preovulatory luteinizing hormone surge. In the present study, we employed brain slice electrophysiology to question whether synaptic ionotropic GABA and glutamate receptor signaling at the GnRH neuron changed at times of negative and positive feedback. We used a well characterized estradiol (E)-treated ovariectomized (OVX) mouse model to replicate negative and positive feedback. Miniature and spontaneous postsynaptic currents (mPSCs and sPSCs) attributable to GABA A and glutamatergic receptor signaling were recorded from GnRH neurons obtained from intact diestrous, OVX, OVX + E (negative feedback), and OVX + E+E (positive feedback) female mice. Approximately 90% of GnRH neurons exhibited spontaneous GABA A -mPSCs in all groups but no significant differences in the frequency or kinetics of mPSCs were found at the times of negative or positive feedback. Approximately 50% of GnRH neurons exhibited spontaneous glutamate mPSCs but again no differences were detected. The same was true for spontaneous PSCs in all cases. These observations indicate that the kinetics of ionotropic GABA and glutamate receptor synaptic transmission to GnRH neurons remain stable across the different estrogen feedback states.

  5. Epidural vs intramuscular administration of lecirelin, a GnRH analogue, for the resolution of follicular cysts in dairy cows.

    Science.gov (United States)

    Rizzo, Annalisa; Annalisa, Rizzo; Campanile, Debora; Debora, Campanile; Mutinati, Maddalena; Maddalena, Mutinati; Minoia, Giuseppe; Giuseppe, Minoia; Spedicato, Massimo; Massimo, Spedicato; Sciorsci, Raffaele Luigi; Luigi, Sciorsci Raffaele

    2011-06-01

    Bovine follicular cysts are an ovarian disorder of dairy cows associated with abnormal estrous behaviour and infertility. The treatment of choice is intramuscular administration of a GnRH analogue, which acts by triggering pituitary release of LH. However, the presence of GnRH and GnRH receptors on spinal cord and ovary in some species, and the kind of innervation of the ovary, let us hypothesize that GnRH and its analogues may also act when administered by epidural route, as happens for other drugs. Therefore the aim of this study was to compare the effects of epidural vs intramuscular administration of lecirelin (a GnRH analogue) on FC regression, estrus detection and pregnancy outcomes. The study was conducted on 220 Friesian cows affected by follicular cysts, divided among 4 groups: Group L(epid) and Group L(im) received, respectively 50 μg of lecirelin in the epidural space and intramuscular; Group C(epid) and Group C(im) were used as control groups. In Group L(epid), estrus induction and pregnancy rates were significantly higher than in Group L(im). The results of this study show that the epidural administration of lecirelin promoted the remission of follicular cysts and an improvement of reproductive parameters compared to intramuscular administration. Thus, an alternative therapeutical approach is available for FC treatment, in order to obtain an easier restoration of the ovarian activity, especially in those cases refractory to classical therapeutic approaches. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Reproductive physiology of a humanized GnRH receptor mouse model: application in evaluation of human-specific analogs.

    Science.gov (United States)

    Tello, Javier A; Kohout, Trudy; Pineda, Rafael; Maki, Richard A; Scott Struthers, R; Millar, Robert P

    2013-07-01

    The human GnRH receptor (GNRHR1) has a specific set of properties with physiological and pharmacological influences not appropriately modeled in laboratory animals or cell-based systems. To address this deficiency, we have generated human GNRHR1 knock-in mice and described their reproductive phenotype. Measurement of pituitary GNRHR1 transcripts from homozygous human GNRHR1 knock-in (ki/ki) mice revealed a severe reduction (7- to 8-fold) compared with the mouse Gnrhr1 in wild-type mice. ¹²⁵I-GnRH binding assays on pituitary membrane fractions corroborated reduced human GNRHR1 protein expression in ki/ki mice, as occurs with transfection of human GNRHR1 in cell lines. Female homozygous knock-in mice displayed normal pubertal onset, indicating that a large reduction in GNRHR1 expression is sufficient for this process. However, ki/ki females exhibited periods of prolonged estrous and/or metestrous and reduced fertility. No impairment was found in reproductive maturity or adult fertility in male ki/ki mice. Interestingly, the serum LH response to GnRH challenge was reduced in both knock-in males and females, indicating a reduced GNRHR1 signaling capacity. Small molecules targeting human GPCRs usually have poor activities at homologous rodent receptors, thus limiting their use in preclinical development. Therefore, we tested a human-specific GnRH1 antagonist, NBI-42902, in our mouse model and demonstrated abrogation of a GnRH1-induced serum LH rise in ki/ki mice and an absence of effect in littermates expressing the wild-type murine receptor. This novel model provides the opportunity to study the human receptor in vivo and for screening the activity of human-specific GnRH analogs.

  7. Withania somnifera aqueous extract facilitates the expression and release of GnRH: In vitro and in vivo study.

    Science.gov (United States)

    Kataria, Hardeep; Gupta, Muskan; Lakhman, Sukhwinder; Kaur, Gurcharan

    2015-10-01

    Ashwagandha (Withania somnifera) has a long history in traditional medicines as an aphrodisiac. It has been known to influence sexual behaviour in animal models but mechanism of action is still unknown. The present study was aimed to investigate the mechanisms by which Ashwagandha extract exert its gonadotropic activities. Due to the complexity of neuroendocrine pathways, there are limited in vitro models available despite the strong demand for such systems to study and predict neuroendocrine effects of chemicals or natural products. Immortalized rat hypothalamic GnV-3 cell line was investigated as a model to screen for neuroendocrine effects of Ashwagandha extract. GnV-3 cells were cultured under different media conditions and evaluated after treatment with Ashwagandha water extract, for GnRH expression and release by immunostaining and ELISA respectively. These cells acquired differentiated morphology, characteristic shape displayed by preoptic GnRH neurons in vivo. In addition, GnV-3 cells exhibited upregulation of plasticity related polysialylated neural cell adhesion molecule (PSA-NCAM) and mature dendrite marker microtubule associated protein (MAP2) as well as GnRH expression and release. Chloroform fraction of the extract proved to exhibit all the bioactive properties as it induced differentiation and upregulated GnRH and MAP2 expression in GnV-3 cells, similar to Ashwagandha extract. Withanone and Withaferin A were found to be present in ASH-WEX and chloroform fraction while Withanone came out to be the major constituent of chloroform fraction. The preliminary in vivo studies in adult male animals showed that ASH-WEX was able to upregulate the GnRH levels although non-significantly. Taken together, this data demonstrate significant morphological and physiological changes in GnV-3 cells after treatment with Ashwagandha extract and may suggest the potential beneficial effects of Ashwagandha on reproductive functions in vivo. Copyright © 2015 Elsevier Ltd

  8. EFECTO DE LA GnRH EN EL PROCESO DEL RECONOCIMIENTO MATERNAL DE LA PREÑEZ SOBRE LA SUPERVIVENCIA EMBRIONARIA EN ALPACAS

    OpenAIRE

    Araínga R., Mariluz; Práctica privada; Leyva V., Víctor; Laboratorio de Reproducción y Obstetricia Veterinaria, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima Perú.; García V., Wilber; Estación Experimental del Centro de Investigación IVITA-Maranganí, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima Perú.; Franco Ll., Enrique; Estación Experimental del Centro de Investigación IVITA-Maranganí, Facultad de Medicina Veterinaria, Universidad Nacional Mayor de San Marcos, Lima Perú.

    2013-01-01

    The effect of GnRH administered around the time of maternal recognition of prenancy on the embryonic survival rate was studied. It was used 67 adult female alpacas sexually receptive to the male, and bearing a preovulatory follicle ≥7mm, detected by rectal ultrasonography. Animals were distributed in three groups: G0 (n=23) as control; G1 (n=22) received 6 µg GnRH on day 4 after ovulation; and G2 (n=22) received 4 µg GnRH on days 8 and 9 after ovulation. The ocurrence of ovulation was confirm...

  9. Efficiency of fixed-time artificial insemination using a progesterone device combined with GnRH or estradiol benzoate in Nellore heifers

    Directory of Open Access Journals (Sweden)

    Vinícius Antônio Pelissari Poncio

    2015-10-01

    Full Text Available he use of estrogens in artificial insemination protocols for cattle is the least expensive and most efficient method currently available. However, the trend to prohibit the use of estrogens for this purpose has made it necessary to find alternatives that replace estrogens without compromising the reproductive performance of the animals. The objective of this study was to evaluate conception rates in Bos indicus beef heifers treated with a progesterone device (P4 combined with GnRH or an estradiol ester. On day 0, pubertal Nellore heifers (n = 100 received an intravaginal device containing 1 g P4 and were randomly divided into two groups. The GnRH group (n = 49 received an intramuscular injection of 100 µg GnRH, while the E2 group (n = 51 received 2 mg estradiol benzoate (EB. The P4 device was removed after 5 (GnRH group or 8 days (E2 group, followed by an injection of 125 µg of the PGF2α, analog cloprostenol. On that occasion, the E2 group received an additional injection of 300 IU eCG. Twenty-four hours later, the GnRH group received a second injection of 125 µg cloprostenol, while the E2 group received 1 mg EB. The heifers were inseminated 72 (GnRH group or 54 hours (E2 group after removal of the P4 device. At the time of insemination, the GnRH group received additionally an injection of 100 µg GnRH. Estrus was monitored during the period of cloprostenol injection until the time of artificial insemination and pregnancy was diagnosed 40 days after insemination by transrectal ultrasonography. The data were analyzed by Fisher’s exact test. The pregnancy rate was 38.8% and 31.4% in the GnRH and E2 groups, respectively (P>0.05. The ovarian condition of the heifers (estrus or anestrus tended to influence (P=0.07 pregnancy rates in the GnRH group, but not in the E2 group. At the time of artificial insemination, 33.3% of heifers in the GnRH group showed signs of estrus versus 88.2% in the E2 group (P<0.05. However, the time of estrus

  10. Day two post retrieval 1500 IUI hCG bolus, progesterone-free luteal support post GnRH agonist trigger - a proof of concept study.

    Science.gov (United States)

    Vanetik, Sharon; Segal, Linoy; Breizman, Tatiana; Kol, Shahar

    2018-02-01

    Small dose of hCG (1500 IU) on the day of oocyte retrieval, followed by daily progesterone administration, is currently the preferred way to secure adequate luteal support following GnRH agonist trigger. In the current proof-of-concept study, we explored the possibility that a bolus of 1500 IU hCG, given two days after oocyte retrieval, may be sufficient to sustain adequate luteal support without additional progesterone treatment. From February 2015 to August 2016, we obtained 44 pregnancies following GnRHa trigger followed by day 2 hCG (1500 IU) support only (study group). Data from these 44 cycles were compared with the latest 44 pregnancies obtained following hCG (6500 IU) trigger followed by conventional progesterone luteal documented (control group). Mean progesterone levels (14 days postoocyte retrieval) in the study and control groups were 197 nmol/l and 173 nmol/l, respectively (NS). Mean E 2 levels (14 days post oocyte retrieval) in the study group was 6937 pmol/l, significantly higher (p hCG, administered 2 days after retrieval, can provide excellent support, without the need to further supplement with progesterone.

  11. A comparative therapeutic management of anoestrus in buffaloes using insulin and GnRH

    Directory of Open Access Journals (Sweden)

    R. D. Purkayastha

    2015-06-01

    Full Text Available Aim: Anoestrus is one of the most common functional disorders of the reproductive cycle in buffaloes. In spite of technical advancement, there is no single cure for the management of anoestrus. Therefore, the aim of this study was to find out the efficacy of gonadotropic releasing hormone (GnRH and metabolic hormone for the management of true anoestrus in buffaloes. Materials and Methods: The experimental animals were selected on the basis of history, gyneco-clinical examinations and progesterone estimation. Deworming was done with Fenbendazole and thereafter mineral mixture was given @ 50 g per animal per day for 10 days in all the selected buffaloes before the start of treatment. The selected buffaloes were randomly divided into four groups (n=25. In Group I, buffaloes were administered 20 μg of buserelin intramuscularly. Buffaloes of Group II were administered long-acting insulin @ 0.25 IU/Kg body weight subcutaneously for 5 consecutive days. In Group III, buffaloes were treated with a combination of insulin and buserelin in the above-mentioned doses whereas buffaloes of Group IV were kept as untreated control. Results: The higher oestrus induction (64% vs. 28% was found in Group III and differed significantly (p<0.05 as compared to control group. The conception rate (69.23% vs. 66.66% was also found higher in Group III but did not differ significantly among the treated groups. The mean time taken for the onset of oestrus was recorded significantly shorter in insulin (8.80±0.69 and GnRH (7.60±0.92 days alone and as compared to other (Group III, 14.43±0.83 and Group IV, 20.57±1.69 days groups. Conclusion: The results of this study indicated better fertility response using Insulin plus Buserelin in true anoestrus buffaloes under field conditions.

  12. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

    Energy Technology Data Exchange (ETDEWEB)

    Camats, N. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, F. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, J.J. [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, J. [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin-Mateo, M. [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, M. Garcia, E-mail: Montserrat.Garcia.Caldes@uab.es [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)

    2009-10-02

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F{sub 0}) with reproductive parameters, and in the somatic cells of the resulting foetuses (F{sub 1}) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  13. EFFECT OF GnRH AND PHOSPHORUS IN DELAYED PUBERTAL SURTI BUFFALO HEIFERS

    Directory of Open Access Journals (Sweden)

    H.B. Dhamsaniya

    2016-06-01

    Full Text Available The study was conducted on eighteen delayed pubertal Surti buffalo heifers, divided into three equal groups (6 in each to evaluate the efficacy of GnRH alone and in combination of phosphorus. The buffalo heifers in Group-I and Group-II were treated with Buserelin acetate (5 ml, IM. Buffalo heifers in Group-II also received additional injection of Toldimphos sodium (10 ml, IM at 3 day interval for 4 times, while buffalo heifers in Group-III served as control. The percentage of induced estrus was highest (83.33% in each treated groups as compared to control group (50%. The mean estrus induction intervals were significantly (P<0.05 shorter in Group-I (20.20 ± 2.18 days and Group-II (18.80 ± 2.32 days as compared to control group (30.24 ± 0.81 days. The conception rate at induced estrus was highest in Group-II (50% followed by Group-I (33.33%. The plasma progesterone levels being significantly lowest on the day of estrus (less than 0.5 ng/ml as compared to pre-treatment days in all groups. The mean total protein and triglycerides levels were differed significantly between the groups on the day of estrus and being significantly higher in Group-II as compared to Group-I and III on that day. A significantly higher level of cholesterol in both treatment groups as compared to the control group during different intervals and also being higher on the day of estrus as compared to pre-treatment days. The mean plasma glucose levels were differed nonsignificantly between and within the treatment and control groups. It is concluded that estrus can be successfully induced in delayed pubertal heifers with the use of GnRH alone and in combination with phosphorus.

  14. Involvement of glucocorticoids in testicular involution after active immunization of boars against GnRH.

    Science.gov (United States)

    Wagner, A; Claus, R

    2004-02-01

    Active GnRH immunization of boars inhibits LH and testicular steroids but the consequences for spermatogenesis are unknown. Six boars were immunized three times against GnRH at 20, 24 and 28 weeks. Another six boars served as controls. Plasma LH and FSH were determined at 28 and 31 weeks. Testosterone and cortisol were determined before killing the pigs at 32 weeks. Tissue samples were taken for histology and fluid from the seminiferous tubuli for steroid determination. Individual germ cells were counted in histological sections. The glucocorticoid receptor (GCR), mitosis of spermatogonia and apoptosis were characterized by immunocytochemistry. Immunization reduced LH and testosterone to base levels whereas FSH was not changed. Testis weight was reduced by 64% due to a loss of Leydig cell cytoplasm (90.3%) and a decrease of tubule diameters (60.6%). Except for A-spermatogonia, all other spermatogenic cells were reduced by about 60%. Mitosis was reduced in immunized boars. Expression of GCRs was limited to spermatogonia and differed between immunized boars (8% of spermatogonia) and controls (2%). In the controls, androgen concentrations in tubular fluid were tenfold higher compared with immunized boars. Cortisol concentrations were of the order of 40 nmol/l both in the tubular fluid and blood plasma. These concentrations did not differ between groups. Apoptosis occurred only in spermatogonia and pachytene spermatocytes and was twofold higher in immunized boars compared with controls. Thus the availability of glucocorticoids in the tubuli and the expression of GCRs initiate apoptosis, which in turn reduces sperm yield. Testosterone is known to be an inhibitor of GCR expression, thus increasing the efficiency of spermatogenesis.

  15. Add-back therapy with GnRH analogues for uterine fibroids.

    Science.gov (United States)

    Moroni, Rafael M; Martins, Wellington P; Ferriani, Rui A; Vieira, Carolina S; Nastri, Carolina O; Candido Dos Reis, Francisco José; Brito, Luiz Gustavo

    2015-03-20

    Uterine fibroids (also known as leiomyomas) are the most common benign pelvic tumours among women. They may be asymptomatic, or may be associated with pelvic symptoms such as bleeding and pain. Medical treatment of this condition is limited and gonadotropin-releasing hormone (GnRH) analogues are the most effective agents. Long-term treatment with such agents, however, is restricted due to their adverse effects. The addition of other medications during treatment with GnRH analogues, a strategy known as add-back therapy, may limit these side effects. There is concern, however, that add-back therapy may also limit the efficacy of the GnRH analogues and that it may not be able to completely prevent their adverse effects. To assess the short-term (within 12 months) effectiveness and safety of add-back therapy for women using GnRH analogues for uterine fibroids associated with excessive uterine bleeding, pelvic pain, or urinary symptoms. We searched electronic databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, LILACS, CINAHL, PsycINFO; and electronic registries of ongoing trials including ClinicalTrials.gov, Current Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform. All searches were from database inception to 16 June 2014. Randomized controlled trials (RCTs) that included women with uterine fibroids experiencing irregular or intense uterine bleeding, cyclic or non-cyclic pelvic pain, or urinary symptoms, and that compared treatment with a GnRH analogue plus add-back therapy versus a GnRH analogue alone or combined with placebo were eligible for inclusion. Two authors independently reviewed the identified titles and abstracts for potentially eligible records. Two review authors reviewed eligible studies and independently extracted data. Two authors independently assessed the studies' risk of bias. They assessed the quality of the

  16. Tonsillar pulsatility before and after surgical decompression for children with Chiari malformation type 1: an application for true fast imaging with steady state precession

    Energy Technology Data Exchange (ETDEWEB)

    Radmanesh, Alireza [University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Washington University School of Medicine, Mallinckrodt Institute of Radiology, St Louis, MO (United States); Greenberg, Jacob K.; Smyth, Matthew D.; Limbrick, David D. [Washington University School of Medicine, Department of Neurosurgery, St Louis, MO (United States); Chatterjee, Arindam; Sharma, Aseem [Washington University School of Medicine, Mallinckrodt Institute of Radiology, St Louis, MO (United States)

    2015-04-01

    We hypothesize that surgical decompression for Chiari malformation type 1 (CM-1) is associated with statistically significant decrease in tonsillar pulsatility and that the degree of pulsatility can be reliably assessed regardless of the experience level of the reader. An Institutional Review Board (IRB)-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study was performed on 22 children with CM-1 (8 males; mean age 11.4 years) who had cardiac-gated true-FISP sequence and phase-contrast cerebrospinal fluid (CSF) flow imaging as parts of routine magnetic resonance (MR) imaging before and after surgical decompression. The surgical technique (decompression with or without duraplasty) was recorded for each patient. Three independent radiologists with different experience levels assessed tonsillar pulsatility qualitatively and quantitatively and assessed peritonsillar CSF flow qualitatively. Results were analyzed. To evaluate reliability, Fleiss kappa for multiple raters on categorical variables and intra-class correlation for agreement in pulsatility ratings were calculated. After surgical decompression, the degree of tonsillar pulsatility appreciably decreased, confirmed by t test, both qualitatively (p values <0.001, <0.001, and 0.045 for three readers) and quantitatively (amount of decrease/p value for three readers 0.7 mm/<0.001, 0.7 mm/<0.001, and 0.5 mm/0.022). There was a better agreement among the readers in quantitative assessment of tonsillar pulsatility (kappa 0.753-0.834), compared to qualitative assessment of pulsatility (kappa 0.472-0.496) and qualitative assessment of flow (kappa 0.056 to 0.203). Posterior fossa decompression with duraplasty led to a larger decrease in tonsillar pulsatility, compared to posterior fossa decompression alone. Tonsillar pulsatility in CM-1 is significantly reduced after surgical decompression. Quantitative assessment of tonsillar pulsatility was more reliable across readers than

  17. Hemodynamics and arteriovenous malformations in cavopulmonary anastomosis: the case for residual antegrade pulsatile flow.

    Science.gov (United States)

    Henaine, Roland; Vergnat, Mathieu; Mercier, Olaf; Serraf, Alain; De Montpreville, Vincent; Ninet, Jean; Bacha, Emile A

    2013-12-01

    Continuous flow in Fontan circulation results in impairment of pulmonary artery endothelial function, increased pulmonary vascular resistance, and, potentially, late failure of Fontan circulation. Bidirectional cavopulmonary shunt is the interim procedure in palliation of patients with single-ventricle physiology, but pulmonary arteriovenous malformations occur in many patients. In a porcine chronic model of cavopulmonary shunt, we studied pulmonary hemodynamics, pulmonary arteriovenous malformation occurrence, and gas exchange capabilities. We hypothesized that residual antegrade pulsatile pulmonary flow may attenuate the deleterious effects of nonpulsatile Fontan-type circulation. Thirty pigs underwent a sham procedure (n = 10, group I), a cavopulmonary shunt with right pulmonary artery ligation (n = 10, group II, nonpulsatile), or a cavopulmonary shunt with proximal right pulmonary artery partial ligation (n = 10, group III, micropulsatile). Three months later, in vivo hemodynamics, blood gas exchange, pulmonary arteriovenous malformation occurrence, and lung histology were assessed. At 3 months, group II right lungs demonstrated significantly increased pulmonary artery pressure, pulmonary vascular resistance, and evidence of pulmonary arteriovenous malformations compared with groups I and III (all P < .001). Group III lungs also showed increased pulmonary artery pressure and pulmonary vascular resistance compared with the sham group, but significantly less than group II. Group III right lungs had the best gas exchange performance, with less histologic changes compared with group II. We developed a viable chronic large animal model of bidirectional cavopulmonary anastomosis. Residual antegrade pulsatile flow in the setting of a cavopulmonary shunt prevents pulmonary arteriovenous malformation formation and attenuates, but does not suppress, the development of pulmonary hypertension. From a clinical standpoint, these data would support keeping a small

  18. Carotid artery stiffness and hemodynamic pulsatility during cognitive engagement in healthy adults: a pilot investigation.

    Science.gov (United States)

    Heffernan, Kevin S; Spartano, Nicole L; Augustine, Jacqueline A; Lefferts, Wesley K; Hughes, William E; Mitchell, Gary F; Jorgensen, Randall S; Gump, Brooks B

    2015-05-01

    The matching of vascular supply to neuronal metabolic demand during cognitive engagement is known as neurovascular coupling (NVC). Arterial stiffness is a prominent determinant of pulsatility in the systemic circulation and may thus indirectly impact NVC. In this pilot investigation, we explored changes in carotid artery stiffness and cerebrovascular hemodynamic pulsatiltiy during cognitive engagement in healthy adults. Twenty-seven adults (age 39 ± 3 years, BMI 24 ± 1 kg/m(2)) underwent Doppler ultrasonography of the common carotid artery (CCA) combined with applanation tonometry to derive (i) CCA elastic modulus (Ep) and β-stiffness index; (ii) CCA flow pulsatility index (PI); (iii) CCA pulse pressure, (iv) CCA augmentation index (AIx). Cerebral PI was assessed using transcranial Doppler at the middle cerebral artery (MCA). All measures were made at rest and during an incongruent Stroop task. CCA PI was reduced (1.75 ± 0.06 to 1.57 ± 0.06, P 0.05) during Stroop. Brachial pulse pressure increased during Stroop (43 ± 1 to 46 ± 1 mm Hg, P 0.05). Similarly, CCA Ep (54.5 ± 5.5 to 53.8 ± 4.9 kPa, P > 0.05) and β-stiffness index (4.4 ± 0.4 to 4.2 ± 0.3 aU, P > 0.05) were unchanged. CCA AIx increased (1 ± 4 to 13 ± 4%, P cognitive engagement. Carotid artery stiffness does not change suggesting that factors other than the dynamic elastic properties of the CCA buffer cerebrovascular hemodynamic pulsatility during cognitive engagement. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Pulsatile Versus Oscillatory Shear Stress Regulates NADPH Oxidase Subunit Expression: Implication for Native LDL Oxidation

    OpenAIRE

    Hwang, Juliana; Ing, Michael H.; Salazar, Adler; Lassègue, Bernard; Griendling, Kathy; Navab, Mohamad; Sevanian, Alex; Hsiai, Tzung K.

    2003-01-01

    Shear stress regulates endothelial nitric oxide and superoxide (O2−·) production, implicating the role of NADPH oxidase activity. It is unknown whether shear stress regulates the sources of reactive species production, consequent low-density lipoprotein (LDL) modification, and initiation of inflammatory events. Bovine aortic endothelial cells (BAECs) in the presence of 50 μg/mL of native LDL were exposed to (1) pulsatile flow with a mean shear stress (τave) of 25 dyne/cm2 and (2) oscillating ...

  20. Fetal umbilical artery Doppler pulsatility index and childhood neurocognitive outcome at 12 years

    OpenAIRE

    Mone, Fionnuala; McConnell, Barbara; Thompson, Andrew; Segurado, Ricardo; Hepper, Peter; Stewart, Moira C.; Dornan, James C; Ong, Stephen; McAuliffe, Fionnuala M.; Shields, Michael D.

    2016-01-01

    OBJECTIVE: To determine whether an elevated fetal umbilical artery Doppler (UAD) pulsatility index (PI) at 28 weeks' gestation, in the absence of fetal growth restriction (FGR) and prematurity, is associated with adverse neurocognitive outcome in children aged 12 years.METHODS: Prospective cohort study, comparing children with a normal fetal UAD PI (<90th centile) (n=110) and those with an elevated PI (≥90th centile) (n=40). UAD was performed at 28, 32 and 34 weeks gestation. At 12 years o...

  1. Pulsatile microfluidics as an analytical tool for determining the dynamic characteristics of microfluidic systems

    DEFF Research Database (Denmark)

    Vedel, Søren; Olesen, Laurits Højgaard; Bruus, Henrik

    2010-01-01

    An understanding of all fluid dynamic time scales is needed to fully understand and hence exploit the capabilities of fluid flow in microfluidic systems. We propose the use of harmonically oscillating microfluidics as an analytical tool for the deduction of these time scales. Furthermore, we......-filled interconnected elastic microfluidic tubes containing a large, trapped air bubble and driven by a pulsatile pressure difference. We demonstrate good agreement between the system-level model and the experimental results, allowing us to determine the dynamic time scales of the system. However, the generic analysis...... can be applied to all microfluidic systems, both ac and dc....

  2. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas

    2007-01-01

    Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... and the GnRH receptor blocker degarelix. Methods Fifty-eight healthy subjects received single subcutaneous or intramuscular injections of 3.75 mg of triptorelin and 170 prostate cancer patients received multiple subcutaneous doses of degarelix of between 120 and 320 mg. All subjects were pooled...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

  3. Serum levels of antimüllerian hormone in early maturing girls before, during, and after suppression with GnRH agonist

    DEFF Research Database (Denmark)

    Hagen, Casper P; Sørensen, Kaspar; Anderson, Richard A

    2012-01-01

    To evaluate whether serum antimüllerian hormone (AMH) levels are affected in early maturing girls, and whether pituitary suppression by long-acting GnRH agonist (GnRH-a) affects AMH.......To evaluate whether serum antimüllerian hormone (AMH) levels are affected in early maturing girls, and whether pituitary suppression by long-acting GnRH agonist (GnRH-a) affects AMH....

  4. Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support

    DEFF Research Database (Denmark)

    Iliodromiti, Stamatina; Blockeel, Christophe; Tremellen, Kelton P

    2013-01-01

    Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?......Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)?...

  5. A comparative study of luteal estradiol pre-treatment in GnRH antagonist protocols and in micro dose flare protocols for poor-responding patients.

    Science.gov (United States)

    Davar, Robab; Rahsepar, Mozhgan; Rahmani, Elham

    2013-01-01

    This study aims to verify if luteal estradiol pre-treatment improves IVF/ICSI outcomes in a GnRH antagonist protocol as compared with a micro dose GnRH agonist protocol in poor-responding patients. A total of 116 IVF/ICSI cycles were included in this prospective randomized single blind clinical trial. The selected women were randomly assigned to receive an estradiol pre-treatment in a GnRH antagonist protocol (daily oral Estradiol Valerate 4 mg preceding the IVF cycle from the 21st day until the first day of the next cycle) or in oral contraceptive pill micro dose GnRH agonist protocol. The patients in the luteal estradiol protocol required more days of stimulation (10.9 ± 1.6 vs. 10.2 ± 1.8) and a greater gonadotropin requirement (3,247.8 ± 634.6 vs. 2,994.8 ± 611 IU), yet similar numbers of oocytes were retrieved and fertilized. There was no significant difference between the two groups in terms of the implantation rates (9.8 vs. 7.9 %) and the clinical pregnancy rates per transfer (16.3 vs. 15.6 %). This study demonstrates that the use of estradiol during a preceding luteal phase in a GnRH antagonist protocol can provide similar IVF outcomes when compared to a micro dose GnRH agonist protocol.

  6. Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3

    Directory of Open Access Journals (Sweden)

    Lund Eiliv

    2009-07-01

    Full Text Available Abstract Background Gonadotropin releasing hormone (GNRH1 triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3. Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs were genotyped and used to identify haplotype-tagging SNPs (htSNPS in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II, European Prospective Investigation on Cancer and Nutrition (EPIC, Multiethnic Cohort (MEC, Nurses' Health Study (NHS, and Women's Health Study (WHS. Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.

  7. The Response of an Elastic Splitter Plate Attached to a Cylinder to Laminar Pulsatile Flow

    CERN Document Server

    Kundu, Anup; Bhardwaj, Rajneesh; Thompson, Mark C

    2016-01-01

    The flow-induced deformation of a thin, elastic splitter plate attached to the rear of a circular cylinder and subjected to laminar pulsatile inflow is investigated. The cylinder and elastic splitter plate are contained within a narrow channel and the Reynolds number is mostly restricted to Re = 100, primarily covering the two-dimensional flow regime. An in-house fluid-structure interaction code is employed for simulations, which couples a sharp-interface immersed boundary method for the fluid dynamics with a finite-element method to treat the structural dynamics. The structural solver is implicitly (two-way) coupled with the flow solver using a partitioned approach. This implicit coupling ensures numerical stability at low structure-fluid density ratios. A power spectrum analysis of the time-varying plate displacement shows that the plate oscillates at more than a single frequency for pulsatile inflow, compared to a single frequency observed for steady inflow. The multiple frequencies obtained for the former...

  8. Enteric-coating of pulsatile-release HPC capsules prepared by injection molding.

    Science.gov (United States)

    Macchi, E; Zema, L; Maroni, A; Gazzaniga, A; Felton, L A

    2015-04-05

    Capsular devices based on hydroxypropyl cellulose (Klucel® LF) intended for pulsatile release were prepared by injection molding (IM). In the present work, the possibility of exploiting such capsules for the development of colonic delivery systems based on a time-dependent approach was evaluated. For this purpose, it was necessary to demonstrate the ability of molded cores to undergo a coating process and that coated systems yield the desired performance (gastric resistance). Although no information was available on the coating of IM substrates, some issues relevant to that of commercially-available capsules are known. Thus, preliminary studies were conducted on molded disks for screening purposes prior to the spray-coating of HPC capsular cores with Eudragit® L 30 D 55. The ability of the polymeric suspension to wet the substrate, spread, start penetrating and initiate hydration/swelling, as well as to provide a gastroresistant barrier was demonstrated. The coating of prototype HPC capsules was carried out successfully, leading to coated systems with good technological properties and able to withstand the acidic medium with no need for sealing at the cap/body joint. Such systems maintained the original pulsatile release performance after dissolution of the enteric film in pH 6.8 fluid. Therefore, they appeared potentially suitable for the development of a colon delivery platform based on a time-dependent approach. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Aneurysm pulsatility after endovascular exclusion: an experimental study using human aortic aneurysms

    Directory of Open Access Journals (Sweden)

    Hussein Amin Orra

    2008-01-01

    Full Text Available OBJECTIVE: To measure the pulsatility of human aneurysms before and after complete exclusion with an endograft. METHOD: Five aortic aneurysms obtained during necropsy were submitted to pulsatile perfusion before and after implantation of a bifurcated endograft. The specimens were contained in a closed chamber filled with saline solution. A vertical tube attached to the chamber was used to measure volume dislocation in each systole. Mural thrombus was kept intact, and the space around the device was filled with human blood. After each experiment, the aneurysm was opened to check for the correct positioning and attachment of the device. RESULTS: The level of the saline column oscillated during pulsation in each case, with respective amplitudes of 17, 16, 13, 7, and 25 cm before the endograft insertion. After the insertion, the amplitudes dropped to 13, 12, 9, 3.5, and 23 cm, respectively. The differences were not significant. During the post-experimental examination, all devices were found to be in position and well attached to the neck and iliacs. No endoleak was detected during perfusion or by visual inspection. CONCLUSION: Pulsation of an endograft is transmitted to the aneurysm wall even in the absence of endoleak, and should not be interpreted as procedural failure.

  10. Correlation between vortices and wall shear stress in a curved artery model under pulsatile flow conditions

    Science.gov (United States)

    Cox, Christopher; Plesniak, Michael W.

    2017-11-01

    One of the most physiologically relevant factors within the cardiovascular system is the wall shear stress. The wall shear stress affects endothelial cells via mechanotransduction and atherosclerotic regions are strongly correlated with curvature and branching in the human vasculature, where the shear stress is both oscillatory and multidirectional. Also, the combined effect of curvature and pulsatility in cardiovascular flows produces unsteady vortices. In this work, our goal is to assess the correlation between multiple vortex pairs and wall shear stress. To accomplish this, we use an in-house high-order flux reconstruction Navier-Stokes solver to simulate pulsatile flow of a Newtonian blood-analog fluid through a rigid 180° curved artery model. We use a physiologically relevant flow rate and generate results using both fully developed and uniform entrance conditions, the latter motivated by the fact that flow upstream to a curved artery may not be fully developed. Under these two inflow conditions, we characterize the evolution of various vortex pairs and their subsequent effect on several wall shear stress metrics. Supported by GW Center for Biomimetics and Bioinspired Engineering.

  11. Pulsatile flow of blood and heat transfer with variable viscosity under magnetic and vibration environment

    Energy Technology Data Exchange (ETDEWEB)

    Shit, G.C., E-mail: gopal_iitkgp@yahoo.co.in; Majee, Sreeparna

    2015-08-15

    Unsteady flow of blood and heat transfer characteristics in the neighborhood of an overlapping constricted artery have been investigated in the presence of magnetic field and whole body vibration. The laminar flow of blood is taken to be incompressible and Newtonian fluid with variable viscosity depending upon temperature with an aim to provide resemblance to the real situation in the physiological system. The unsteady flow mechanism in the constricted artery is subjected to a pulsatile pressure gradient arising from systematic functioning of the heart and from the periodic body acceleration. The numerical computation has been performed using finite difference method by developing Crank–Nicolson scheme. The results show that the volumetric flow rate, skin-friction and the rate of heat transfer at the wall are significantly altered in the downstream of the constricted region. The axial velocity profile, temperature and flow rate increases with increase in temperature dependent viscosity, while the opposite trend is observed in the case of skin-friction and flow impedance. - Highlights: • We have investigated the pulsatile MHD flow of blood and heat transfer in arteries. • The influence of periodic body acceleration has been taken into account. • The temperature dependent viscosity of blood is considered. • The variable viscosity has an increasing effect on blood flow and heat transfer. • The overall temperature distribution enhances in the presence of magnetic field.

  12. Chronotherapeutically Modulated Pulsatile System of Valsartan Nanocrystals-an In Vitro and In Vivo Evaluation.

    Science.gov (United States)

    Biswas, Nikhil; Kuotsu, Ketousetuo

    2017-02-01

    The objective was to improve the dissolution of valsartan by developing valsartan nanocrystals and design a pulsed release system for the chronotherapy of hypertension. Valsartan nanocrystals were prepared by sonication-anti-solvent precipitation method and lyophilized to obtain dry powder. Nanocrystals were directly compressed to minitablets and coated to achieve pulsatile valsartan release. Pharmacokinetic profiles of optimized and commercial formulations were compared in rabbit model. The mean particle size and PDI of the optimized nanocrystal batch V4 was reported as 211 nm and 0.117, respectively. DSC and PXRD analysis confirmed the crystalline nature of valsartan in nanocrystals. The dissolution extent of valsartan was markedly enhanced with both nanocrystals and minitablets as compared to pure valsartan irrespective of pH of the medium. Core minitablet V4F containing 5% w/w polyplasdone XL showed quickest release of valsartan, over 90% within 15 min. Coated formulation CV4F showed two spikes in release profile after successive lag times of 235 and 390 min. The pharmacokinetic study revealed that the bioavailability of optimized formulation (72.90%) was significantly higher than the commercial Diovan tablet (30.18%). The accelerated stability studies showed no significant changes in physicochemical properties, release behavior, and bioavialability of CV4F formulation. The formulation was successfully designed to achieve enhanced bioavailability and dual pulsatile release. Bedtime dosing will more efficiently control the circadian spikes of hypertension in the morning.

  13. Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation.

    Science.gov (United States)

    Popovych, Oleksandr V; Lysyansky, Borys; Rosenblum, Michael; Pikovsky, Arkady; Tass, Peter A

    2017-01-01

    High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson's disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS.

  14. Elderly depression diagnostic of diabetic patients by brain tissue pulsatility imaging

    Science.gov (United States)

    Hachemi, Mélouka Elkateb; Remeniéras, Jean-pierre; Desmidt, Thomas; Camus, Vincent; Tranquart, François

    2010-01-01

    Pulsatile motion of brain parenchyma results from cardiac and breathing cycles and consists in a rapid displacement in systole, with slow diastolic recovery. Based on the vascular depression concept and recent studies where a correlation was found between cerebral haemodynamics and depression in the elderly, we emitted the hypothesis that tissue brain motion due to perfusion is correlated to elderly depression associated with cardiovascular risk factors. Tissue Pulsatlity Imaging (TPI) is a new ultrasound technique developed firstly at the University of Washington to assess the brain tissue motion. We used TPI technique to measure the brain displacement of two groups of elderly patients with diabetes as a vascular risk factor. The first group is composed of 11 depressed diabetic patients. The second group is composed of 12 diabetic patients without depressive symptoms. Transcranial acquisitions were performed with a 1.8 MHz ultrasound phased array probe through the right temporal bone window. The acquisition of six cardiac cycles was realized on each patient with a frame rate of 23 frames/s. Displacements estimation was performed by off-line analysis. A significant decrease in brain pulsatility was observed in the group of depressed patients compared to the group of non depressed patients. Mean displacement magnitude was about 44±7 μm in the first group and 68±13 μm in the second group.

  15. Computational fluid dynamics analysis and PIV validation of a bionic vortex flow pulsatile LVAD.

    Science.gov (United States)

    Xu, Liang; Yang, Ming; Ye, Lin; Dong, Zhaopeng

    2015-01-01

    Hemocompatibility is highly affected by the flow field in Left Ventricular Assistant Devices (LVAD). An asymmetric inflow and outflow channel arrangement with a 45° intersection angle with respect to the blood chamber is proposed to approximate the vascular structure of the aorta and left atrium on the left ventricle. The structure is expected to develop uninterruptible vortex flow state which is similar to the flow state in human left ventricle. The Computational Fluid Dynamics (CFD) asymmetric model is simulated using ANSYS workbench. To validate the velocity field calculated by CFD, a Particle Image Velocimetry (PIV) experiment is conducted. The CFD results show that the proposed blood chamber could generate a shifting vortex flow that would be redirected to the aorta during ejection to form a persistent recirculating flow state, which is similar to the echocardiographic flow state in left ventricle. Both the PIV and the CFD results show the development of a persistent vortex during the pulsatile period. Comparison of the qualitative flow pattern and quantitative probed velocity histories in a pulsatile period shows a good agreement between the CFD and PIV data. The goal of developing persistent quasi intra-ventricle vortex flow state in LVAD is realized.

  16. Biological time series analysis using a context free language: applicability to pulsatile hormone data.

    Directory of Open Access Journals (Sweden)

    Dennis A Dean

    Full Text Available We present a novel approach for analyzing biological time-series data using a context-free language (CFL representation that allows the extraction and quantification of important features from the time-series. This representation results in Hierarchically AdaPtive (HAP analysis, a suite of multiple complementary techniques that enable rapid analysis of data and does not require the user to set parameters. HAP analysis generates hierarchically organized parameter distributions that allow multi-scale components of the time-series to be quantified and includes a data analysis pipeline that applies recursive analyses to generate hierarchically organized results that extend traditional outcome measures such as pharmacokinetics and inter-pulse interval. Pulsicons, a novel text-based time-series representation also derived from the CFL approach, are introduced as an objective qualitative comparison nomenclature. We apply HAP to the analysis of 24 hours of frequently sampled pulsatile cortisol hormone data, which has known analysis challenges, from 14 healthy women. HAP analysis generated results in seconds and produced dozens of figures for each participant. The results quantify the observed qualitative features of cortisol data as a series of pulse clusters, each consisting of one or more embedded pulses, and identify two ultradian phenotypes in this dataset. HAP analysis is designed to be robust to individual differences and to missing data and may be applied to other pulsatile hormones. Future work can extend HAP analysis to other time-series data types, including oscillatory and other periodic physiological signals.

  17. Kisspeptin/Gpr54-independent GnRH activity in Kiss1 and Gpr54 mutant mice

    OpenAIRE

    Chan, Yee-Ming; Broder-Fingert, Sarabeth; Wong, Kai Mee; Seminara, Stephanie B.

    2009-01-01

    The kisspeptin/Gpr54 signaling pathway plays a critical role in reproduction by stimulating the secretion of GnRH, yet mice carrying mutations in Kiss1 (which encodes kisspeptin) or Gpr54 exhibit partial sexual maturation. For instance, a proportion of female Kiss1−/− and Gpr54−/− mice exhibit vaginal oestrus, and some male Kiss1−/− and Gpr54−/− mice exhibit spermatogenesis.

  18. GnRH antagonist and letrozole co-treatment in diminished ovarian reserve patients: a proof-of-concept study.

    Science.gov (United States)

    Olgan, Safak; Humaidan, Peter

    2017-03-01

    The current study aimed to investigate the effects of luteal gonadotropin-releasing hormone (GnRH) antagonist pretreatment on the outcomes of diminished ovarian reserve (DOR) patients who were treated using a FSH/letrozole/GnRH antagonist (FLA) protocol. Thus, patients who had luteal GnRH antagonist pretreatment (AFLA) prior to stimulation were compared to patients who had the FLA protocol, only. An electronic database was used to identify patients and stimulation characteristics. Women who had a total antral follicle count (AFC) of protocol were compared to 76 cycles using a FLA protocol, only. The total gonadotropin dose, duration of stimulation, and peak estradiol levels were comparable between the groups (p>0.05). However, the AFLA group had significantly more metaphase-2 (MII) oocytes (p=0.009), a higher oocyte maturity rate (MII/total oocytes) (p=0.029), and a higher mature oocyte yield (MII/AFC) (p=0.020) with more cleaved embryos (p=0.036), and a significantly reduced number of canceled cycles (26.7% vs. 44.7%; p=0.048). The clinical pregnancy rate per cycle was 22.2% vs. 13.2% (p=0.195) in the AFLA and FLA groups, respectively. Interestingly, a subgroup analysis including ESHRE Bologna criteria poor responder patients showed that the luteal administration of GnRH antagonist resulted in better outcomes when compared with the FLA protocol alone. In conclusion, luteal GnRH antagonist pretreatment improves ovarian stimulation parameters and reproductive outcomes in poor ovarian reserve IVF patients. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  19. Circadian Control of the Estrogenic Circuits Regulating GnRH Secretion and the Preovulatory Luteinizing Hormone Surge

    Directory of Open Access Journals (Sweden)

    Lance J Kriegsfeld

    2012-05-01

    Full Text Available Female reproduction requires the precise temporal organization of interacting, estradiol-sensitive neural circuits that converge to optimally drive hypothalamo-pituitary-gonadal (HPG axis functioning. In mammals, the master circadian pacemaker in the suprachaismatic nucleus (SCN of the anterior hypothalamus coordinates reproductively-relevant neuroendocrine events necessary to maximize reproductive success. Likewise, in species where periods of fertility are brief, circadian oversight of reproductive function ensures that estradiol-dependent increases in sexual motivation coincide with ovulation. Across species, including humans, disruptions to circadian timing (e.g., through rotating shift work, night shift work, poor sleep hygiene lead to pronounced deficits in ovulation and fecundity. Despite the well-established roles for the circadian system in female reproductive functioning, the specific neural circuits and neurochemical mediators underlying these interactions are not fully understood. Most work to date has focused on the direct and indirect communication from the SCN to the GnRH system in control of the preovulatory LH surge. However, the same clock genes underlying circadian rhythms at the cellular level in SCN cells are also common to target cell populations of the SCN, including the GnRH neuronal network. Exploring the means by which the master clock synergizes with subordinate clocks in GnRH cells and its upstream modulatory systems represents an exciting opportunity to further understand the role of endogenous timing systems in female reproduction. Herein we provide an overview of the state of knowledge regarding interactions between the circadian timing system and estradiol-sensitive neural circuits driving GnRH secretion and the preovulatory LH surge.

  20. Improvement of chloride transport defect by gonadotropin-releasing hormone (GnRH in cystic fibrosis epithelial cells.

    Directory of Open Access Journals (Sweden)

    Nathalie Benz

    Full Text Available Cystic fibrosis (CF, the most common autosomal recessive disease in Caucasians, is due to mutations in the CFTR gene. F508del, the most frequent mutation in patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER and its traffic to the plasma membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a Cl(- channel function despite a short half-life. Pharmacological treatments may target the F508del-CFTR defect directly by binding to the mutant protein or indirectly by altering cellular proteostasis, and promote its plasma membrane targeting and stability. We previously showed that annexine A5 (AnxA5 directly binds to F508del-CFTR and, when overexpressed, promotes its membrane stability, leading to the restoration of some Cl(- channel function in cells. Because Gonadotropin-Releasing Hormone (GnRH increases AnxA5 expression in some cells, we tested it in CF cells. We showed that human epithelial cells express GnRH-receptors (GnRH-R and that GnRH induces an AnxA5 overexpression and an increased Cl(- channel function in F508del-CFTR cells, due to an increased stability of the protein in the membranes. Beside the numerous physiological implications of the GnRH-R expression in epithelial cells, we propose that a topical use of GnRH is a potential treatment in CF.

  1. Improvement of chloride transport defect by gonadotropin-releasing hormone (GnRH) in cystic fibrosis epithelial cells.

    Science.gov (United States)

    Benz, Nathalie; Le Hir, Sophie; Norez, Caroline; Kerbiriou, Mathieu; Calvez, Marie-Laure; Becq, Frédéric; Trouvé, Pascal; Férec, Claude

    2014-01-01

    Cystic fibrosis (CF), the most common autosomal recessive disease in Caucasians, is due to mutations in the CFTR gene. F508del, the most frequent mutation in patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER) and its traffic to the plasma membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a Cl(-) channel function despite a short half-life. Pharmacological treatments may target the F508del-CFTR defect directly by binding to the mutant protein or indirectly by altering cellular proteostasis, and promote its plasma membrane targeting and stability. We previously showed that annexine A5 (AnxA5) directly binds to F508del-CFTR and, when overexpressed, promotes its membrane stability, leading to the restoration of some Cl(-) channel function in cells. Because Gonadotropin-Releasing Hormone (GnRH) increases AnxA5 expression in some cells, we tested it in CF cells. We showed that human epithelial cells express GnRH-receptors (GnRH-R) and that GnRH induces an AnxA5 overexpression and an increased Cl(-) channel function in F508del-CFTR cells, due to an increased stability of the protein in the membranes. Beside the numerous physiological implications of the GnRH-R expression in epithelial cells, we propose that a topical use of GnRH is a potential treatment in CF.

  2. Behavior of feral horses in response to culling and GnRH immunocontraception

    Science.gov (United States)

    Ransom, Jason I.; Powers, Jenny G.; Garbe, Heidi M.; Oehler, Michael W.; Nett, Terry M.; Baker, Dan L.

    2014-01-01

    Wildlife management actions can alter fundamental behaviors of individuals and groups,which may directly impact their life history parameters in unforeseen ways. This is especially true for highly social animals because changes in one individual’s behavior can cascade throughout its social network. When resources to support populations of social animals are limited and populations become locally overabundant, managers are faced with the daunting challenge of decreasing population size without disrupting core behavioral processes. Increasingly, managers are turning to fertility control technologies to supplement culling in efforts to suppress population growth, but little is quantitatively known about how either of these management tools affects behavior. Gonadotropin releasing hormone (GnRH) is a small neuropeptide that performs an obligatory role in mammalian reproduction and has been formulated into the immunocontraceptive GonaCon-BTM. We investigated the influences of this vaccine on behavior of feral horses (Equus caballus) at Theodore Roosevelt National Park, North Dakota, USA, for a year preceding and a year following nonlethal culling and GnRH-vaccine treatment. We observed horses during the breeding season and found only minimal differences in time budget behaviors of free-ranging female feral horses treated with GnRH and those treated with saline. The differences observed were consistent with the metabolic demands of pregnancy and lactation. We observed similar social behaviors between treatment groups, reflecting limited reproductive behavior among control females due to high rates of pregnancy and suppressed reproductive behavior among treated females due to GnRH-inhibited ovarian activity. In the treatment year, band stallion age was the only supported factor influencing herding behavior (P stallions decreased 50.7% following treatment and culling (P reproductive, and agonistic behavior in the year following culling and treatment (P < 0.04). These

  3. Kisspeptin/Gpr54-independent GnRH activity in Kiss1 and Gpr54 mutant mice

    Science.gov (United States)

    Chan, Yee-Ming; Broder-Fingert, Sarabeth; Wong, Kai Mee; Seminara, Stephanie B.

    2009-01-01

    The kisspeptin/Gpr54 signaling pathway plays a critical role in reproduction by stimulating the secretion of GnRH, yet mice carrying mutations in Kiss1 (which encodes kisspeptin) or Gpr54 exhibit partial sexual maturation. For instance, a proportion of female Kiss1−/− and Gpr54−/− mice exhibit vaginal oestrus, and some male Kiss1−/− and Gpr54−/− mice exhibit spermatogenesis. To characterise this partial sexual maturation, we examined the vaginal cytology of female Kiss1−/− and Gpr54−/− mice over time. Nearly all mutant mice eventually enter oestrus, then spontaneously transition from oestrus to dioestrus and back to oestrus again. These transitions are not associated with ovulation, and the frequency of these transitions increases with age. The oestrus exhibited by female Kiss1−/− and Gpr54−/− mice was disrupted by administration of the competitive GnRH antagonist acyline, which also resulted in lower uterine weights and, in Kiss1−/− mice, lower serum FSH and LH concentrations. Similarly, male Kiss1−/− and Gpr54−/− mice treated with acyline had smaller testicular sizes and absence of mature sperm. In addition to examining intact Kiss1−/− and Gpr54−/− mice, we also assessed the effects of acyline on gonadotrophin concentrations in gonadectomised mice. Gonadectomy resulted in a significant increase in serum FSH concentrations in male Gpr54−/− and Kiss1−/− mice. Acyline administration to gonadectomised Kiss1−/− and Gpr54−/− male mice lowered serum FSH and LH concentrations significantly. In contrast to males, gonadectomy did not result in significant gonadotrophin changes in female Kiss1−/− and Gpr54−/− mice, but acyline administration was followed by a decrease in LH concentrations. These results demonstrate that, while kisspeptin signaling is critical for the high levels of GnRH activity required for normal sexual maturation and for ovulation, Kiss1−/− and Gpr54−/− mice retain some

  4. Clinical Effectiveness of Centrifugal Pump to Produce Pulsatile Flow During Cardiopulmonary Bypass in Patients Undergoing Cardiac Surgery

    NARCIS (Netherlands)

    Gu, Y. John; van Oeveren, Willem; Mungroop, Hubert E.; Epema, Anne H.; den Hamer, Inez J.; Keizer, Jorrit J.; Leuvenink, Ron P.; Mariani, Massimo A.; Rakhorst, Gerhard

    Although the centrifugal pump has been widely used as a nonpulsatile pump for cardiopulmonary bypass (CPB), little is known about its performance as a pulsatile pump for CPB, especially on its efficacy in producing hemodynamic energy and its clinical effectiveness. We performed a study to evaluate

  5. Increased pulsatile movement of the hindbrain in syringomyelia associated with the Chiari malformation: cine-MRI with presaturation bolus tracking

    Energy Technology Data Exchange (ETDEWEB)

    Terae, S. [Hokkaido Univ. School of Medicine, Sapporo (Japan). Dept. of Radiology; Miyasaka, K. [Hokkaido Univ. School of Medicine, Sapporo (Japan). Dept. of Radiology; Abe, S. [Hokkaido Univ. School of Medicine, Sapporo (Japan). Dept. of Radiology; Abe, H.; Tashiro, K. [Hokkaido Univ. School of Medicine, Sapporo (Japan). Dept. of Neurology

    1994-02-01

    Cine-MRI with presaturation bolus tracking was used in patients with syringomyelia associated with a Chiari malformation to study pulsatile movement of the hindbrain, cervical spinal cord, cerebrospinal fluid and the fluid within the syrinx. Nine patients had 13 examinations, 6 preoperative, 3 after syringosubarachnoid shunting and 4 after posterior fossa decompression. Five controls were also examined. Dynamic display of the acquired images demonstrated downward displacement of the presaturation bolus on the cerebellar tonsils and medulla oblongata (or upper cervical cord) at the C1 level in all preoperative examinations and in two patients after syringo-subarachnoid shunting but with residual foramen magnum obstruction. Downward displacement of the bolus on the cervical spinal cord was also demonstrated in 7 examinations, but not observed in the controls. Thus, the hindbrain-spinal cord axis showed larger pulsatile movements in patients with foramen magnum obstruction. Based on these observations and a review of the literature, a new theory on the mode of extension of syringomyelia, emphasising the role of increased pulsatile movement of the hindbrain-spinal cord axis is proposed: that the pulsatile movements, together with a one-way valve mechanism in the syrinx cavity act as a ``vacuum-pump`` to enlarge the syrinx. (orig.)

  6. Pulsatile drug delivery to ileo-colonic segments by structured incorporation of disintegrants in pH-responsive polymer coatings

    NARCIS (Netherlands)

    Schellekens, R.C.A.; Stellaard, F.; Mitrovic, D.; Stuurman, F.E.; Kosterink, J.G.W.; Frijlink, H.W.

    2008-01-01

    Conventional pH-responsive coatings used for oral drug delivery to the lower parts of the gastro-intestinal tract often show a poor performance. A new system for site-specific pulsatile delivery in the ileo-colonic regions is described. The system is based on the non-percolating incorporation of

  7. Multidetector CT imaging of mechanical prosthetic heart valves: quantification of artifacts with a pulsatile in-vitro model

    NARCIS (Netherlands)

    Symersky, Petr; Budde, Ricardo P. J.; Westers, Paul; de Mol, Bas A. J. M.; Prokop, Mathias

    2011-01-01

    Multidetector computed tomography (MDCT) can detect the cause of prosthetic heart valve (PHV) dysfunction but is hampered by valve-induced artifacts. We quantified artifacts of four PHV using a pulsatile in-vitro model and assessed the relation to leaflet motion and valve design. A Medtronic Hall

  8. Multidetector CT imaging of mechanical prosthetic heart valves : quantification of artifacts with a pulsatile in-vitro model

    NARCIS (Netherlands)

    Symersky, Petr; Budde, Ricardo P. J.; Westers, Paul; de Mol, Bas A. J. M.; Prokop, Mathias

    2011-01-01

    Objectives Multidetector computed tomography (MDCT) can detect the cause of prosthetic heart valve (PHV) dysfunction but is hampered by valve-induced artifacts. We quantified artifacts of four PHV using a pulsatile in-vitro model and assessed the relation to leaflet motion and valve design. Methods

  9. Rationale, scope, and 20-year experience of vascular surgical training with lifelike pulsatile flow models.

    Science.gov (United States)

    Eckstein, Hans-Henning; Schmidli, Jürg; Schumacher, Hardy; Gürke, Lorenz; Klemm, Klaus; Duschek, Nikolaus; Meile, Toni; Assadian, Afshin

    2013-05-01

    Vascular surgical training currently has to cope with various challenges, including restrictions on work hours, significant reduction of open surgical training cases in many countries, an increasing diversity of open and endovascular procedures, and distinct expectations by trainees. Even more important, patients and the public no longer accept a "learning by doing" training philosophy that leaves the learning curve on the patient's side. The Vascular International (VI) Foundation and School aims to overcome these obstacles by training conventional vascular and endovascular techniques before they are applied on patients. To achieve largely realistic training conditions, lifelike pulsatile models with exchangeable synthetic arterial inlays were created to practice carotid endarterectomy and patch plasty, open abdominal aortic aneurysm surgery, and peripheral bypass surgery, as well as for endovascular procedures, including endovascular aneurysm repair, thoracic endovascular aortic repair, peripheral balloon dilatation, and stenting. All models are equipped with a small pressure pump inside to create pulsatile flow conditions with variable peak pressures of ~90 mm Hg. The VI course schedule consists of a series of 2-hour modules teaching different open or endovascular procedures step-by-step in a standardized fashion. Trainees practice in pairs with continuous supervision and intensive advice provided by highly experienced vascular surgical trainers (trainer-to-trainee ratio is 1:4). Several evaluations of these courses show that tutor-assisted training on lifelike models in an educational-centered and motivated environment is associated with a significant increase of general and specific vascular surgical technical competence within a short period of time. Future studies should evaluate whether these benefits positively influence the future learning curve of vascular surgical trainees and clarify to what extent sophisticated models are useful to assess the level of

  10. Kisspeptin-gpr54 signaling at the GnRH neuron is necessary for negative feedback regulation of luteinizing hormone secretion in female mice.

    Science.gov (United States)

    Yeo, Shel-Hwa; Clarkson, Jenny; Herbison, Allan E

    2014-01-01

    Kisspeptin-Gpr54 signaling is critical for regulating the activity of gonadotropin-releasing hormone (GnRH) neurons in mammals. Previous studies have shown that the negative feedback mechanism is disrupted in global Gpr54-null mutants. The present investigation aimed to determine (1) if a lack of cyclical estrogen exposure of the GnRH neuronal network in the life-long hypogonadotropic Gpr54-null mice contributed to their failed negative feedback mechanism and (2) the cellular location of disrupted kisspeptin-Gpr54 signaling. Plasma luteinizing hormone (LH) concentrations were determined in individual adult female mice when intact, following ovariectomy (OVX) and in response to an acute injection of 17β-estradiol (E2). Control mice exhibited a characteristic rise in LH after OVX that was suppressed by acute E2. Global Gpr54-null mice failed to exhibit any post-OVX increase in LH or response to E2. Adult female global Gpr54-null mice given a cyclical regimen of estradiol for three cycles prior to OVX also failed to exhibit any post-OVX increase in LH or response to E2. To address whether Gpr54 signaling at the GnRH neuron itself was necessary for the failed response to OVX in global Gpr54-null animals, adult female mice with a GnRH neuron-selective deletion of Gpr54 were examined. These mice also failed to exhibit any post-OVX increase in LH or response to E2. These experiments demonstrate defective negative feedback in global Gpr54-null mice that cannot be attributed to a lack of prior exposure of the GnRH neuronal network to cyclical estradiol. The absence of negative feedback in GnRH neuron-selective Gpr54-null mice demonstrates the necessity of direct kisspeptin signaling at the GnRH neuron for this mechanism to occur. © 2014 S. Karger AG, Basel.

  11. Temperature affects sexual maturation through the control of kisspeptin, kisspeptin receptor, GnRH and GTH subunit gene expression in the grass puffer during the spawning season.

    Science.gov (United States)

    Shahjahan, Md; Kitahashi, Takashi; Ando, Hironori

    2017-03-01

    Water temperature is an environmental factor of primary importance that influences reproductive function in fish. To understand the molecular and physiological mechanisms underlying the regulation of reproduction by temperature, we examined changes in expression of genes encoding kisspeptin (kiss2), kisspeptin receptor (kiss2r) and three gonadotropin-releasing hormones (gnrh1, gnrh2 and gnrh3) in the brain and genes encoding gonadotropin (GTH) subunits (gpa, fshb and lhb) in the pituitary of grass puffer exposed to a low temperature (14°C), normal temperature (21°C) and high temperature (28°C) for 7days. In addition, the plasma levels of cortisol were examined after exposed to three temperature conditions. The gonadosomatic index was significantly decreased in both low and high temperature conditions. The levels of kiss2 and kiss2r mRNAs were significantly decreased at both low and high temperature conditions compared to normal temperature (control) condition. gnrh1 but not gnrh2 were significantly decreased in both temperature conditions, while gnrh3 showed a decreasing tendency in low temperature. Consequently, the levels of fshb and lhb mRNAs were significantly decreased in both low and high temperature conditions. Interestingly, the plasma levels of cortisol were significantly increased in low temperature but remain unchanged in high temperature, suggesting that the fish were under stress in the low temperature conditions but not in the high temperature conditions. Taken together, the present results indicate that anomalous temperature have an inhibitory effect on reproductive function through suppressing kiss2/kiss2r/gnrh1/fshb and lhb expression and these changes may occur in a normal physiological response as well as in a malfunctional stress response. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Pulsatile flow decreases gaseous micro-bubble filtering properties of oxygenators without integrated arterial filters during cardiopulmonary bypass

    Science.gov (United States)

    Milano, Aldo D.; Dodonov, Mikhail; Onorati, Francesco; Menon, Tiziano; Gottin, Leonardo; Malerba, Giovanni; Mazzucco, Alessandro; Faggian, Giuseppe

    2013-01-01

    OBJECTIVES Cardiopulmonary bypass (CPB) has a risk of embolic injury with an important role of gaseous micro-bubbles (GMBs), coming from CPB-circuit. Pulsatile perfusion (PP) can provide specific conditions for supplementary GMB-activity with respect to non-pulsatile (NP). We aimed to test GMB-filtering properties of three modern oxygenators under pulsatile and non-pulsatile conditions. METHODS Seventy-eight patients undergoing on-pump myocardial revascularization were randomized prospectively into three equal groups according to the oxygenator model used during CPB. Terumo Capiox-FX25, Sorin Synthesis or Maquet Quadrox-i-Adult membrane oxygenators were tested. Each group was divided equally to undergo PP or NP. GMBs were counted by means of a GAMPT-BCC200 bubble-counter with two probes placed at preoxygenator and arterial post-filter positions. Results were evaluated in terms of GMB-volume, GMB-number, amount of large over-ranged GMBs, a series of filtering indices and major neurological outcomes. RESULTS PP decreased GMB-filtering properties of the tested oxygenators. Those with integrated filters (CAPIOX-FX25 and SYNTHESIS) did not show significant differences between perfusion groups, while QUADROX-i oxygenator with external arterial filter showed significantly higher GMB-volume (P bubbles (P filtering capacity of all circuits with both types of perfusion, no important differences in clinical outcomes and major neurological events were observed. CONCLUSIONS Pulsatile flow decreases gaseous micro-bubble filtering properties of oxygenators without integrated arterial filters during CPB. PP requires specially designed circuit components to avoid the risk of additional GMB delivery. PMID:23842758

  13. Diagnostic utility of magnetic resonance imaging and magnetic resonance angiography in the radiological evaluation of pulsatile tinnitus.

    Science.gov (United States)

    Shweel, Mohamed; Hamdy, Balegh

    2013-01-01

    Our aim was to assess the diagnostic utility of magnetic resonance imaging with complimentary magnetic resonance angiography (MRI/MRA) in the radiological evaluation of patients with pulsatile tinnitus (PT). The present study was retrospectively conducted on 27 patients with pulsatile tinnitus. All patients showed normal otoscopic findings and were evaluated with magnetic resonance imaging (MRI) with complimentary magnetic resonance angiography (MRA), 9/27 (33.3%) patients were investigated by CT, and 12/27 (44.4%) were evaluated by angiography. All patients' clinical investigation was reviewed to discard systemic causes of PT. All hard copies of MRI/MRA studies were evaluated. MRI/MRA detected the underlying etiology of subjective pulsatile tinnitus (PT) in 11/27 patients (40.7%), and 16/27 patients (59.5%) showed normal MRI/MRA examination. The most common cause was dural arteriovenous malformation (AFM) in 4/27 (14.8%) patients, high jugular bulbus in 2/27 (7.4%), aneurysm of internal carotid artery in 1/27 (3.7%), aberrant internal carotid artery in 1/27 (3.7%), vertebral artery hypoplasia in 2/27 (7.4%), and glomus tumor in 1/27 (3.7%). The statistical results of the present study showed that MRI/MRA had the following: 80% sensitivity, 88% specificity, 86% accuracy, 85% PPV, 83% NPV, and 15% error percentage for diagnosis of PT. MRI/MRA was an effective radiological imaging method in detecting the underlying pathology of pulsatile tinnitus. Magnetic resonance may be considered a first line diagnostic imaging modality in the assessment of subjective pulsatile tinnitus. © 2013 Elsevier Inc. All rights reserved.

  14. A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

    Science.gov (United States)

    Vemula, Sateesh Kumar

    2015-12-01

    A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

  15. Extracellular Signal-Regulated Kinase (ERK Activation and Mitogen-Activated Protein Kinase Phosphatase 1 Induction by Pulsatile Gonadotropin-Releasing Hormone in Pituitary Gonadotrophs

    Directory of Open Access Journals (Sweden)

    Haruhiko Kanasaki

    2012-01-01

    Full Text Available The frequency of gonadotropin-releasing hormone (GnRH pulse secreted from the hypothalamus differently regulates the expressions of gonadotropin subunit genes, luteinizing hormone β (LHβ and follicle-stimulating hormone β (FSHβ, in the pituitary gonadotrophs. FSHβ is preferentially stimulated at slower GnRH pulse frequencies, whereas LHβ is preferentially stimulated at more rapid pulse frequencies. Several signaling pathways are activated, including mitogen-activated protein kinase (MAPK, protein kinase C, calcium influx, and calcium-calmodulin kinases, and these may be preferentially regulated under certain conditions. Previous studies demonstrated that MAPK pathways, especially the extracellular signal-regulated kinase (ERK, play an essential role for induction of gonadotropin subunit gene expression by GnRH, whereas, MAPK phosphatases (MKPs inactivate MAPKs through dephosphorylation of threonine and/or tyrosine residues. MKPs are also induced by GnRH, and potential feedback regulation between MAPK signaling and MKPs within the GnRH signaling pathway is evident in gonadotrophs. In this paper, we reviewed and mainly focused on our observations of the pattern of ERK activation and the induction of MKP by different frequencies of GnRH stimulation.

  16. Physicochemical effects enhance surfactant transport in pulsatile motion of a semi-infinite bubble.

    Science.gov (United States)

    Pillert, Jerina E; Gaver, Donald P

    2009-01-01

    In this study, we investigate the sorption of pulmonary surfactant (Infasurf, Ony, Buffalo, NY) occurring at the air-liquid interface of a semi-infinite finger of air as it oscillates and progresses along a small rigid tube (1 mm inner diameter) occluded with a surfactant-doped solution of concentrations C=0.1, 0.05, or 0.01 mg/mL. This simple experimental model of pulmonary airway reopening is designed to examine how altering the fluid flow field may lower reopening pressures and lead to a reduction in airway wall damage that is associated with the mechanical ventilation of an obstructed pulmonary system in airways of the deep lung with depleted endogenous and little exogenous surfactant. We analyzed a range of pulsatile flow scenarios by varying the oscillation frequency (0surfactant transport and adsorption. This result suggests that imposing high frequency, low amplitude oscillations during airway reopening will help to diminish ventilator-induced lung injury.

  17. New insights into mammalian signaling pathways using microfluidic pulsatile inputs and mathematical modeling.

    Science.gov (United States)

    Sumit, M; Takayama, S; Linderman, J J

    2017-01-23

    Temporally modulated input mimics physiology. This chemical communication strategy filters the biochemical noise through entrainment and phase-locking. Under laboratory conditions, it also expands the observability space for downstream responses. A combined approach involving microfluidic pulsatile stimulation and mathematical modeling has led to deciphering of hidden/unknown temporal motifs in several mammalian signaling pathways and has provided mechanistic insights, including how these motifs combine to form distinct band-pass filters and govern fate regulation under dynamic microenvironment. This approach can be utilized to understand signaling circuit architectures and to gain mechanistic insights for several other signaling systems. Potential applications include synthetic biology and biotechnology, in developing pharmaceutical interventions, and in developing lab-on-chip models.

  18. Non-invasive Measurement of Pressure Gradients in Pulsatile Flow using Ultrasound

    DEFF Research Database (Denmark)

    Olesen, Jacob Bjerring; Traberg, Marie Sand; Pihl, Michael Johannes

    2013-01-01

    This paper demonstrates how pressure gradients in a pulsatile flow environment can be measured non-invasively using ultrasound. The proposed method relies on vector velocity fields acquired from ultrasound data. 2-D flow data are acquired at 18-23 frames/sec using the Transverse Oscillation...... approach. Pressure gradients are calculated from the measured velocity fields using the Navier-Stokes equation. Velocity fields are measured during constant and pulsating flow on a carotid bifurcation phantom and on a common carotid artery in-vivo. Scanning is performed with a 5 MHz BK8670 linear...... transducer using a BK Medical 2202 UltraView Pro Focus scanner. The calculated pressure gradients are validated through a finite element simulation of the constant flow model. The geometry of the flow simulation model is reproduced using MRI data, thereby providing identical flow domains in measurement...

  19. A comparison of Newtonian and non-Newtonian models for pulsatile blood flow simulations

    Science.gov (United States)

    Husain, Iqbal; Labropulu, Fotini; Langdon, Chris; Schwark, Justin

    2013-04-01

    Mathematical modeling of blood flows in the arteries is an important and challenging problem. This study compares several non-Newtonian blood models with the Newtonian model in simulating pulsatile blood flow through two three-dimensional models of an arterial stenosis and an aneurysm. Four non-Newtonian blood models, namely the Power Law, the Casson, the Carreau, and the Generalized Power Law, as well as the Newtonian model of blood viscosity, are used to investigate the flow effects induced by these different blood constitutive equations. The aim of this study is three-fold: firstly, to investigate the variation in wall shear stress in an artery with a stenosis or aneurysm at different flow rates and degrees of severity; secondly, to compare the various blood models and hence quantify the differences between the models and judge their significance; and lastly, to determine whether the use of the Newtonian blood model is appropriate over a wide range of shear rates.

  20. Superior canal dehiscence with tegmen defect revealed by otoscopy: Video clip demonstration of pulsatile tympanic membrane.

    Science.gov (United States)

    Castellucci, Andrea; Brandolini, Cristina; Piras, Gianluca; Fernandez, Ignacio Javier; Giordano, Davide; Pernice, Carmine; Modugno, Giovanni Carlo; Pirodda, Antonio; Ferri, Gian Gaetano

    2018-02-01

    Superior canal dehiscence is a pathologic condition of the otic capsule acting as aberrant window of the inner ear. It results in reduction of inner ear impedance and in abnormal exposure of the labyrinthine neuroepithelium to the action of the surrounding structures. The sum of these phenomena leads to the onset of typical cochleo-vestibular symptoms and signs. Among them, pulsatile tinnitus has been attributed to a direct transmission of intracranial vascular activities to labyrinthine fluids. We present the first video-otoscopic documentation of spontaneous pulse-synchronous movements of the tympanic membrane in two patients with superior canal dehiscence. Pulsating eardrum may represent an additional sign of third-mobile window lesion. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Pulsatile flow through a tube containing rigid and distensible sections. [Artery prosthetic tubing

    Energy Technology Data Exchange (ETDEWEB)

    Daly, B.J.

    1976-01-01

    It is common surgical pactice to replace or bypass defective sections of artery with prosthetic tubing that is stiffer than the natural artery. This abrupt variation in elasticity produces distortions of the adjacent flow field that could contribute to the failure of connective sutures or the dislodgement of thrombi, resulting in embolisms downstream. However, by the proper choice of prosthesis diameter one should be able to minimize these adverse effects. A numerical technique has been developed to study the pulsatile flow of blood from a natural artery into a rigid tube of arbitrary diameter. This method is used to investigate the effects of variations in rigid tube diameter on the flow development at the juncture with the distensible artery. The computation procedure is an extension of the arbitrary lagrangian eulerian (ALE) method.

  2. A viscoelastic fluid-structure interaction model for carotid arteries under pulsatile flow.

    Science.gov (United States)

    Wang, Zhongjie; Wood, Nigel B; Xu, Xiao Yun

    2015-05-01

    In this study, a fluid-structure interaction model (FSI) incorporating viscoelastic wall behaviour is developed and applied to an idealized model of the carotid artery under pulsatile flow. The shear and bulk moduli of the arterial wall are described by Prony series, where the parameters can be derived from in vivo measurements. The aim is to develop a fully coupled FSI model that can be applied to realistic arterial geometries with normal or pathological viscoelastic wall behaviour. Comparisons between the numerical and analytical solutions for wall displacements demonstrate that the coupled model is capable of predicting the viscoelastic behaviour of carotid arteries. Comparisons are also made between the solid only and FSI viscoelastic models, and the results suggest that the difference in radial displacement between the two models is negligible. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Implantable batteryless device for on-demand and pulsatile insulin administration

    Science.gov (United States)

    Lee, Seung Ho; Lee, Young Bin; Kim, Byung Hwi; Lee, Cheol; Cho, Young Min; Kim, Se-Na; Park, Chun Gwon; Cho, Yong-Chan; Choy, Young Bin

    2017-04-01

    Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

  4. PIV Measurement of Pulsatile Flows in 3D Curved Tubes Using Refractive Index Matching Method

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Hyeon Ji; Ji, Ho Seong; Kim, Kyung Chun [Pusan Nat’l Univ., Busan (Korea, Republic of)

    2016-08-15

    Three-dimensional models of stenosis blood vessels were prepared using a 3D printer. The models included a straight pipe with axisymmetric stenosis and a pipe that was bent 10° from the center of stenosis. A refractive index matching method was utilized to measure accurate velocity fields inside the 3D tubes. Three different pulsatile flows were generated and controlled by changing the rotational speed frequency of the peristaltic pump. Unsteady velocity fields were measured by a time-resolved particle image velocimetry method. Periodic shedding of vortices occurred and moves depended on the maximum velocity region. The sizes and the positions of the vortices and symmetry are influenced by mean Reynolds number and tube geometry. In the case of the bent pipe, a recirculation zone observed at the post-stenosis could explain the possibility of blood clot formation and blood clot adhesion in view of hemodynamics.

  5. The use of transcranial Doppler pulsatility index to guide hyperosmolar therapy.

    Science.gov (United States)

    Al-Jehani, Hosam M; Marcoux, Judith; Angle, Mark R; Teitelbaum, Jeanne S

    2012-10-01

    Management of intracranial hypertension is a major cornerstone of neurocritical care. Apart from traumatic brain injury, there are no clear guidelines for intracranial pressure (ICP) monitoring. The insertion of ICP monitors is an invasive procedure with inherent risks and could be contraindicated in case of severe coagulopathy. The transcranial Doppler (TCD) pulsatility index (PI) has emerged as a surrogate marker for ICP. This is a technical report with illustrative cases on the use of PI in the management of high ICP, as a guide for optimal dosing of hyperosmolar agents we use in our institution. The use of TCD PI is a useful adjunct to guide the use of hyperosmolar therapy in various conditions with raised intracranial hypertension. We will discuss the combination of the PI determination with an anatomical evaluation of the optic nerve diameter to eliminate confounding factors in PI determination.

  6. Effect of couple stresses on the pulsatile flow through a constricted annulus

    Science.gov (United States)

    Srinivasacharya, D.; Srikanth, D.

    2008-11-01

    In this Note, the pulsatile flow of an incompressible couple stress fluid through an annulus with mild constriction at the outer wall is considered. This configuration is intended as a simple model for studying blood flow in a stenosed artery when a catheter is inserted into it. An analytical expression in terms of Bessel functions of the first and second kind is obtained for the velocity component. The impedance (resistance to the flow) and wall shear stress are calculated and their variation with respect to the couple stress fluid parameter, height of the constriction and size of the catheter on the impedance and wall shear stress is studied graphically. It is observed that increase in the catheter size increases the resistance to the flow as well as the wall shear stress while the trend is reversed in case of couple stress fluid parameter. To cite this article: D. Srinivasacharya, D. Srikanth, C. R. Mecanique 336 (2008).

  7. Pulsatile lavage irrigator tip, a rare radiolucent retained foreign body in the pelvis: a case report

    Directory of Open Access Journals (Sweden)

    Archdeacon Michael T

    2011-05-01

    Full Text Available Abstract Retained foreign bodies after surgery have the potential to cause serious medical complications for patients and bring fourth serious medico-legal consequences for surgeons and hospitals. Standard operating room protocols have been adopted to reduce the occurrence of the most common retained foreign bodies. Despite these precautions, radiolucent objects and uncounted components/pieces of instruments are at risk to be retained in the surgical wound. We report the unusual case of a retained plastic pulsatile lavage irrigator tip in the surgical wound during acetabulum fracture fixation, which was subsequently identified on routine postoperative computed tomography. Revision surgery was required in order to remove the retained object, and the patient had no further complications.

  8. Accurate quantification of steady and pulsatile flow with segmented k-space magnetic resonance velocimetry

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H.; Halliburton, S.S.; Chatzimavroudis, G.P. [Laboratory of Biofluid Mechanics and Cardiovascular Imaging, Department of Chemical Engineering, Cleveland State University, 1960 East 24th Street, Stilwell Hall 455, Cleveland, OH 44115-2425 (United States); Section of Cardiovascular Imaging, Division of Radiology, The Cleveland Clinic Foundation, Cleveland, OH (United States); Moore, J.R.; Simonetti, O.P. [Magnetic Resonance Division, Siemens Medical Solutions, Chicago, IL (United States); Schvartzman, P.R.; White, R.D. [Section of Cardiovascular Imaging, Division of Radiology, The Cleveland Clinic Foundation, Cleveland, OH (United States)

    2002-09-01

    Conventional non-segmented magnetic resonance phase velocity mapping (MRPVM) is an accurate but relatively slow velocimetric technique. Therefore, the aim of this study was to evaluate the accuracy of the much faster segmented k-space MRPVM in quantifying flow. The axial velocity was measured in four straight tubes (inner diameter: 5.6-26.2 mm), using a segmented MRPVM sequence with seven lines of k-space per segment. The flow rate and flow volume were accurately quantified (errors<5%) under steady (r{sup 2}=0.99) and pulsatile flow (r{sup 2}=0.98), respectively. The measured velocity profiles and flow rates from the segmented sequence agreed with those from the non-segmented (p>0.05). Changing the slice thickness or the field of view did not affect the accuracy of the measurements. The results of this study suggest that fast, segmented MRPVM can be used for accurate flow quantification. (orig.)

  9. Long-term durability test of axial-flow ventricular assist device under pulsatile flow.

    Science.gov (United States)

    Nishida, Masahiro; Kosaka, Ryo; Maruyama, Osamu; Yamane, Takashi; Shirasu, Akio; Tatsumi, Eisuke; Taenaka, Yoshiyuki

    2017-03-01

    A long-term durability test was conducted on a newly developed axial-flow ventricular assist device (VAD) with hydrodynamic bearings. The mock circulatory loop consisted of a diaphragm pump with a mechanical heart valve, a reservoir, a compliance tank, a resistance valve, and flow paths made of polymer or titanium. The VAD was installed behind the diaphragm pump. The blood analog fluid was a saline solution with added glycerin at a temperature of 37 °C. A pulsatile flow was introduced into the VAD over a range of flow rates to realize a positive flow rate and a positive pressure head at a given impeller rotational speed, yielding a flow rate of 5 L/min and a pressure of 100 mmHg. Pulsatile flow conditions were achieved with the diastolic and systolic flow rates of ~0 and 9.5 L/min, respectively, and an average flow rate of ~5 L/min at a pulse rate of 72 bpm. The VAD operation was judged by not only the rotational speed of the impeller, but also the diastolic, systolic, and average flow rates and the average pressure head of the VAD. The conditions of the mock circulatory loop, including the pulse rate of the diaphragm pump, the fluid temperature, and the fluid viscosity were maintained. Eight VADs were tested with testing periods of 2 years, during which they were continuously in operation. The VAD performance factors, including the power consumption and the vibration characteristics, were kept almost constant. The long-term durability of the developed VAD was successfully demonstrated.

  10. Relationship Between Brain Pulsatility and Cerebral Perfusion Pressure: Replicated Validation Using Different Drivers of CPP Change.

    Science.gov (United States)

    Calviello, Leanne A; de Riva, Nicolás; Donnelly, Joseph; Czosnyka, Marek; Smielewski, Peter; Menon, David K; Zeiler, Frederick A

    2017-12-01

    Determination of relationships between transcranial Doppler (TCD)-based spectral pulsatility index (sPI) and pulse amplitude (AMP) of intracranial pressure (ICP) in 2 groups of severe traumatic brain injury (TBI) patients (a) displaying plateau waves and (b) with unstable mean arterial pressure (MAP). We retrospectively reviewed patients with severe TBI and continuous TCD monitoring displaying either plateau waves or unstable MAP from 1992 to 1998. We utilized linear and nonlinear regression techniques to describe both cohorts: cerebral perfusion pressure (CPP) versus AMP, CPP versus sPI, mean ICP versus ICP AMP, mean ICP versus sPI, and AMP versus sPI. Nonlinear regression techniques were employed to analyze the relationships with CPP. In plateau wave and unstable MAP patients, CPP versus sPI displayed an inverse nonlinear relationship (R 2 = 0.820 vs. R 2 = 0.610, respectively), with the CPP versus sPI relationship best modeled by the following function in both cases: PI = a + (b/CPP). Similarly, in both groups, CPP versus AMP displayed an inverse nonlinear relationship (R 2 = 0.610 vs. R 2 = 0.360, respectively). Positive linear correlations were displayed in both the plateau wave and unstable MAP cohorts between: ICP versus AMP, ICP versus sPI, AMP versus sPI. There is an inverse relationship through nonlinear regression between CPP versus AMP and CPP versus sPI display. This provides evidence to support a previously-proposed model of TCD pulsatility index. ICP shows a positive linear correlation with AMP and sPI, which is also established between AMP and sPI.

  11. Analysis of high gradient magnetic field effects on distribution of nanoparticles injected into pulsatile blood stream

    Energy Technology Data Exchange (ETDEWEB)

    Reza Habibi, Mohammad, E-mail: mohammad_habibi_4@yahoo.com [Mechanical Engineering Department, K.N.Toosi University of Technology, Tehran (Iran, Islamic Republic of); Ghassemi, Majid; Hossien Hamedi, Mohammad [Mechanical Engineering Department, K.N.Toosi University of Technology, Tehran (Iran, Islamic Republic of)

    2012-04-15

    Magnetic nanoparticles are widely used in a wide range of applications including data storage materials, pharmaceutical industries as magnetic separation tools, anti-cancer drug carriers and micro valve applications. The purpose of the current study is to investigate the effect of a non-uniform magnetic field on bio-fluid (blood) with magnetic nanoparticles. The effect of particles as well as mass fraction on flow field and volume concentration is investigated. The governing non-linear differential equations, concentration and Navier-stokes are coupled with the magnetic field. To solve these equations, a finite volume based code is developed and utilized. A real pulsatile velocity is utilized as inlet boundary condition. This velocity is extracted from an actual experimental data. Three percent nanoparticles volume concentration, as drug carrier, is steadily injected in an unsteady, pulsatile and non-Newtonian flow. A power law model is considered for the blood viscosity. The results show that during the systole section of the heartbeat when the blood velocity increases, the magnetic nanoparticles near the magnetic source are washed away. This is due to the sudden increase of the hydrodynamic force, which overcomes the magnetic force. The probability of vein blockage increases when the blood velocity reduces during the diastole time. As nanoparticles velocity injection decreases (longer injection time) the wall shear stress (especially near the injection area) decreases and the retention time of the magnetic nanoparticles in the blood flow increases. - Highlights: Black-Right-Pointing-Pointer At the systole time nanoparticles were washed away and concentration decreases. Black-Right-Pointing-Pointer Increasing injection velocity increases the shear stress on upper wall. Black-Right-Pointing-Pointer With decreasing blood velocity nanoparticles remain in flow for longer time. Black-Right-Pointing-Pointer Magnetic nanoparticles aggregation couldn't change

  12. Seasonal and pulsatile dynamics of thyrotropin and leptin in mares maintained under a constant energy balance.

    Science.gov (United States)

    Buff, P R; Messer, N T; Cogswell, A M; Johnson, P J; Keisler, D H; Ganjam, V K

    2007-11-01

    The objective of this study was to determine if seasonal and/or pulsatile variations occur in plasma concentrations of thyrotropin (TSH) and leptin in mares while maintaining a constant energy balance. Blood samples were collected every 20 min during a 24h period in winter and again in summer from six Quarter Horse type mares. Plasma concentrations of TSH, leptin, and T(4) were determined by radioimmunoassay. No differences were observed in body weight between winter (388.1+/-12.5 kg) and summer (406.2+/-12.5 kg; P=0.11). Plasma concentrations of TSH were greater in the summer (2.80+/-0.07 ng/ml) when compared to winter (0.97+/-0.07 ng/ml; P<0.001). Pulse frequency of TSH was not different between winter (6.17+/-0.78 pulses/24h) and summer (5.33+/-0.78 pulses/24h; P=0.49). Mean TSH pulse amplitude, pulse area, and area under the curve were all greater in summer compared to winter (3.11+/-0.10 ng/ml versus 1.20+/-0.10 ng/ml, 24.86+/-0.10 ng/ml min versus 13.46+/-1.90 ng/ml min, 3936+/-72.93 ng/ml versus 1284+/-72.93 ng/ml, respectively; P<0.01). Mean concentrations of leptin were greater in summer (2.48+/-0.17 ng/ml) compared to winter (0.65+/-0.17 ng/ml; P<0.001). Pulsatile secretion patterns of leptin were not observed in any horses during experimentation. Mean concentrations of T(4) were greater in winter (20.3+/-0.4 ng/ml) compared to summer (18.2+/-0.4 ng/ml; P<0.001). These seasonal differences between winter and summer provide evidence of possible seasonal regulation of TSH and leptin.

  13. Attenuation by hypocalcemia of pulsatile growth hormone secretion in conscious male rats.

    Science.gov (United States)

    Minamitani, N; Chihara, K; Iwasaki, J; Matsukura, S; Fujita, T

    1982-12-01

    The effect of hypocalcemia following parathyroidectomy (PTX) on growth hormone (GH) secretion was investigated in unrestrained, unanesthetized male rats bearing chronically implanted indwelling cannulae. During a 6-hour period, starting at about 10 a.m., control rats with a serum calcium (Ca) value of 8.11 +/- 0.38 mg/dl (mean +/- SEM) 2 weeks after sham-operation showed secretory bursts of GH similar to those observed in conscious intact rats. Under hypocalcemia of 4.88 +/- 0.32 mg/dl 2 weeks after PTX, GH secretory episodes were completely suppressed throughout the study. Plasma prolactin (PRL) levels were also decreased in PTX rats as compared with those of sham-operated rats. Daily food intake and body weight gain as well as serum T4 levels in PTX rats were not different from those of sham-operated and intact rats. Pituitary GH content of PTX rats was significantly lower than that of sham-operated and control rats. Pulsatile GH secretion was partially restored in PTX rats by raising serum Ca to 8.43 +/- 0.27 mg/dl through feeding with high Ca diet containing 7% Ca. Immediately after intravenous injection of antisomatostatin sheep serum, pulsatile GH surges recovered in PTX rats despite hypocalcemia of 4.48 +/- 0.74 mg/dl. The mean plasma 6-hour GH levels were significantly higher than those of normal sheep-serum-treated PTX rats (p less than 0.001). These findings suggest that the episodic release of GH is suppressed in hypocalcemic rats after PTX, at least partially via circulating endogenous somatostatin.

  14. Redução da primeira dose de GnRH em vacas holandesas de alta produção sincronizadas com Ovsynch ou Heatsynch

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    Flávio Aragon Lima

    2010-04-01

    Full Text Available The objective of this study was to evaluate the effect of treatment with 10 or 20 µg of GnRH and type of FTAI protocols (Ovsynch and Heatsynch on pregnancy rate of lactating dairy cows submitted to the synchronization at FTAI (n = 581. The animals were distributed among four treatments, allocated factorial design 2x2: Treat 1- Ovsynch (20 µg GnRH on D0; PGF on D7; 10 µg GnRH on D9 and FTAI on D10; n = 141, Treat 2- ½ Ovsynch (10 µg GnRH on D0; PGF on D7; 10 µg GnRH on D9 and FTAI on D10; n = 159, Treat 3- Heatsynch (20 µg GnRH on D0; PGF on D7; 1 mg EB on D8 and FTAI on D10; n = 147 and Treat 4- ½ Heatsynch (10 µg GnRH on D0; PGF on D7; 1 mg EB on D8 and FTAI on D10; n = 134. The Group Ovsynch (Treat 1 and 2 presented greater pregnancy rate than Group Heatsynch (Treat 3 and 4 at 28 days (45.7% (137/300 and 39.9% (112/281, respectively; P = 0.07 and at 56 days of gestation (41.0% (123/300 and 34.2% (96/281, respectively; P = 0.06. There were no statistical difference (P >; 0.10 on pregnancy rate at 28 (44.4% (128/288 vs 41.3% (121/293; P = 0.50 and 56 days (38.2% (110/288 vs 37.2% (109/293; P = 0.68 between the dosages of the GnRH. The pregnancies losses (between 28 and 56 days were not different between the FTAI protocols and GnRH dosage (P >; 0.10. We concluded that the Ovsynch protocol presented greater pregnancy rate at FTAI than Heatsynch protocol and the administration of 10 µg of buserelin Acetate, at the beginning of these protocols did not decrease the efficiency of FTAI protocols in high-yielding Holstein cows.

  15. Effect of short-term and prolonged stress on the biosynthesis of gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) in the hypothalamus and GnRHR in the pituitary of ewes during various physiological states.

    Science.gov (United States)

    Ciechanowska, M; Łapot, M; Antkowiak, B; Mateusiak, K; Paruszewska, E; Malewski, T; Paluch, M; Przekop, F

    2016-11-01

    Using an ELISA assay, the levels of GnRH and GnRHR were analysed in the preoptic area (POA), anterior (AH) and ventromedial hypothalamus (VM), stalk/median eminence (SME); and GnRHR in the anterior pituitary gland (AP) of non-breeding and breeding sheep subjected to short-term or prolonged stress. The ELISA study was supplemented with an analysis of plasma LH concentration. Short-term footshock stimulation significantly increased GnRH levels in hypothalamus in both seasons. Prolonged stress elevated or decreased GnRH concentrations in the POA and the VM, respectively during anoestrus, and lowered GnRH amount in the POA-hypothalamus of follicular-phase sheep. An up-regulation of GnRHR levels was noted in both, anoestrous and follicular-phase animals. In the non-breeding period, a prolonged stress procedure increased GnRHR biosynthesis in the VM and decreased it in the SME and AP, while in the breeding time the quantities of GnRHR were significantly lower in the whole hypothalamus. In follicular-phase ewes the fluctuations of GnRH and GnRHR levels under short-term and prolonged stress were reflected in the changes of LH secretion, suggesting the existence of a direct relationship between GnRH and GnRH-R biosynthesis and GnRH/LH release in this period. The study showed that stress was capable of modulating the biosynthesis of GnRH and GnRHR; the pattern of changes was dependent upon the animal's physiological state and on the time course of stressor application. The obtained results indicate that the disturbances of gonadotropin secretion under stress conditions in sheep may be due to a dysfunction of GnRH and GnRHR biosynthetic pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Sustainable Food & Sustainable Economics

    OpenAIRE

    Alvarez, Mavis Dora

    2012-01-01

    Cuba today is immersed in a very intense process of perfecting its agricultural production structures with the goal of making them more efficient and sustainable in their economic administration and in their social and environmental management. Agricultural cooperatives in Cuba have the responsibility of producing on 73% of the country's farmland. Their contributions are decisive to developing agricultural production and to ensuring more and better food for the population, in addition to redu...

  17. Direct Actions of Kisspeptins on GnRH Neurons Permit Attainment of Fertility but are Insufficient to Fully Preserve Gonadotropic Axis Activity

    Science.gov (United States)

    León, Silvia; Barroso, Alexia; Vázquez, María J.; García-Galiano, David; Manfredi-Lozano, María; Ruiz-Pino, Francisco; Heras, Violeta; Romero-Ruiz, Antonio; Roa, Juan; Schutz, Günther; Kirilov, Milen; Gaytan, Francisco; Pinilla, Leonor; Tena-Sempere, Manuel

    2016-01-01

    Kisspeptins, ligands of the receptor, Gpr54, are potent stimulators of puberty and fertility. Yet, whether direct kisspeptin actions on GnRH neurons are sufficient for the whole repertoire of their reproductive effects remains debatable. To dissect out direct vs. indirect effects of kisspeptins on GnRH neurons in vivo, we report herein the detailed reproductive/gonadotropic characterization of a Gpr54 null mouse line with selective re-introduction of Gpr54 expression only in GnRH cells (Gpr54−/−Tg; rescued). Despite preserved fertility, adult rescued mice displayed abnormalities in gonadal microstructure, with signs of precocious ageing in females and elevated LH levels with normal-to-low testosterone secretion in males. Gpr54−/−Tg rescued mice showed also altered gonadotropin responses to negative feedback withdrawal, while luteinizing hormone responses to various gonadotropic regulators were variably affected, with partially blunted relative (but not absolute) responses to kisspeptin-10, NMDA and the agonist of tachykinin receptors, NK2R. Our data confirm that direct effects of kisspeptins on GnRH cells are sufficient to attain fertility. Yet, such direct actions appear to be insufficient to completely preserve proper functionality of gonadotropic axis, suggesting a role of kisspeptin signaling outside GnRH cells. PMID:26755241

  18. Magnetic resonance guided focused ultrasound surgery of uterine fibroids-The tissue effects of GnRH agonist pre-treatment

    Energy Technology Data Exchange (ETDEWEB)

    Smart, O.C. [Department of Academic Obstetrics and Gynaecology, St. Mary' s Hospital and Imperial College School of Medicine, Praed Street, London W2 1NY (United Kingdom); Department of Magnetic Resonance Imaging, St. Mary' s Hospital and Imperial College School of Medicine, Praed Street, London W2 1NY (United Kingdom); Hindley, J.T. [Department of Academic Obstetrics and Gynaecology, St. Mary' s Hospital and Imperial College School of Medicine, Praed Street, London W2 1NY (United Kingdom); Regan, L. [Department of Academic Obstetrics and Gynaecology, St. Mary' s Hospital and Imperial College School of Medicine, Praed Street, London W2 1NY (United Kingdom); Gedroyc, W.M.W. [Department of Magnetic Resonance Imaging, St. Mary' s Hospital and Imperial College School of Medicine, Praed Street, London W2 1NY (United Kingdom)]. E-mail: w.gedroyc@imperial.ac.uk

    2006-08-15

    Objective: The purpose of this study was to determine the ablative effect of magnetic resonance guided focused ultrasound (MRgFUS) on fibroid tissue following the administration of gonadotrophin releasing hormone (GnRH) agonist. Study design: Fifty women with clinically symptomatic uterine fibroids were treated. Those with uterine diameter of 10 cm or greater were given 3 months pre-treatment with GnRH agonists. Data regarding number of ultrasound sonications, Joules of energy delivered and volume of thermal destruction was recorded. Results: Twenty-seven subjects were given GnRH agonist therapy before MRgFUS and 23 women underwent MRgFUS without pre-treatment. All patients in both study groups completed MR guided FUS as an outpatient procedure with no device related adverse events reported. In the group of women who received GnRH agonists, the volume of ablation was significantly larger than that in the control group (0.06 cm{sup 3} versus 0.03 cm{sup 3}, P < 0.05), per Joule of energy applied. Conclusion: The use of GnRH agonists potentiates the thermal effects of MRgFUS in women undergoing treatment of uterine fibroids.

  19. Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Matsuno, Y.; Yamashita, Y.; Takahashi, M. [Dept. of Radiology, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Katabuchi, H.; Okamura, H. [Dept. of Gynecology and Obstetrics, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Kitano, Y.; Shimamura, T. [Dept. of Gynecology and Obstetrics, Amakusa Chuou General Hospital, Hondo (Japan)

    1999-11-01

    Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29{+-}0.11). The size ratio for the hypointense tumors was 0.82{+-}0.14, and 0.82{+-}0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

  20. Lactobacillus rhamnosus accelerates zebrafish backbone calcification and gonadal differentiation through effects on the GnRH and IGF systems.

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    Matteo A Avella

    Full Text Available Endogenous microbiota play essential roles in the host's immune system, physiology, reproduction and nutrient metabolism. We hypothesized that a continuous administration of an exogenous probiotic might also influence the host's development. Thus, we treated zebrafish from birth to sexual maturation (2-months treatment with Lactobacillus rhamnosus, a probiotic species intended for human use. We monitored for the presence of L. rhamnosus during the entire treatment. Zebrafish at 6 days post fertilization (dpf exhibited elevated gene expression levels for Insulin-like growth factors -I and -II, Peroxisome proliferator activated receptors -α and -β, VDR-α and RAR-γ when compared to untreated-10 days old zebrafish. Using a gonadotropin-releasing hormone 3 GFP transgenic zebrafish (GnRH3-GFP, higher GnRH3 expression was found at 6, 8 and 10 dpf upon L. rhamnosus treatment. The same larvae exhibited earlier backbone calcification and gonad maturation. Noteworthy in the gonad development was the presence of first testes differentiation at 3 weeks post fertilization in the treated zebrafish population -which normally occurs at 8 weeks- and a dramatic sex ratio modulation (93% females, 7% males in control vs. 55% females, 45% males in the treated group. We infer that administration of L. rhamnosus stimulated the IGF system, leading to a faster backbone calcification. Moreover we hypothesize a role for administration of L. rhamnosus on GnRH3 modulation during early larval development, which in turn affects gonadal development and sex differentiation. These findings suggest a significant role of the microbiota composition on the host organism development profile and open new perspectives in the study of probiotics usage and application.

  1. Testosterone production in response to exogenous gonadotropin releasing hormone (GnRH challenge) depends on social environment and color polymorphism.

    Science.gov (United States)

    Cain, Kristal E; Pryke, Sarah R

    2017-04-01

    Testosterone is an important mediator of behavior, morphology and physiology. A cascade of signals regulates the amount of testosterone (T) circulating in the plasma; in response to stimulus the hypothalamus releases gonadotropin-releasing hormone (GnRH), which triggers secretion of gonadotropins from the pituitary, stimulating the synthesis and release of T from the gonads. Previous work has shown that changes to the social environment can alter circulating T-levels, which may have important fitness consequences, but it is currently unclear whether these changes are due to alterations in the signal from the brain, or changes in the ability of the pituitary and gonads to respond to this signal. Further, the strength and direction of response to a changing environment may differ according to life-history strategy. Species with genetically determined alternative strategies offer a pathway for examining these differences. Here we use a finch with a genetically determined polymorphism, the Gouldian finch (Erythrura gouldiae), to determine whether T-levels change in response to social environment. We also use injections of GnRH to determine whether these changes are due to alterations in the ability of the pituitary and gonads to respond to this signal. We found that social environment (presence of females) had a rapid effect on male circulating T-levels, and that this difference was reflected in responsiveness to GnRH. We observed no overall morph differences in T-levels, but we did observe morph differences in the pattern of T secretion across environments, and morph differences in the repeatability of T-levels across time and environment. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Eel Kisspeptins: Identification, Functional Activity, and Inhibition on both Pituitary LH and GnRH Receptor Expression

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    Jérémy Pasquier

    2018-01-01

    Full Text Available The European eel (Anguilla anguilla presents a blockade of sexual maturation at a prepubertal stage due to a deficient production of gonadotropins. We previously initiated, in the eel, the investigation of the kisspeptin system, one of the major gatekeepers of puberty in mammals, and we predicted the sequence of two Kiss genes. In the present study, we cloned and sequenced Kiss1 and Kiss2 cDNAs from the eel brain. The tissue distributions of Kiss1 and Kiss2 transcripts, as investigated by quantitative real-time PCR, showed that both genes are primarily expressed in the eel brain and pituitary. The two 10-residue long sequences characteristic of kisspeptin, eel Kp1(10 and Kp2(10, as well as two longer sequences, predicted as mature peptides, eel Kp1(15 and Kp2(12, were synthesized and functionally analyzed. Using rat Kiss1 receptor-transfected Chinese hamster ovary cells, we found that the four synthesized eel peptides were able to induce [Ca2+]i responses, indicating their ability to bind mammalian KissR-1 and to activate second messenger pathways. In primary culture of eel pituitary cells, all four peptides were able to specifically and dose-dependently inhibit lhβ expression, without any effect on fshβ, confirming our previous data with heterologous kisspeptins. Furthermore, in this eel in vitro system, all four peptides inhibited the expression of the type 2 GnRH receptor (gnrh-r2. Our data revealed a dual inhibitory effect of homologous kisspeptins on both pituitary lhβ and gnrh-r2 expression in the European eel.

  3. Characterization and differential expression of three GnRH forms during reproductive development in cultured turbot Schophthalmus maximus

    Science.gov (United States)

    Zhao, Chunyan; Xu, Shihong; Feng, Chengcheng; Liu, Yifan; Yang, Yang; Wang, Yanfeng; Xiao, Yongshuang; Song, Zongcheng; Liu, Qinghua; Li, Jun

    2017-10-01

    Turbots (Schophthalmus maximus), one of the most important economic marine flatfish species, fail to undergo final spawning and spermiation naturally under artificial farming conditions. In vertebrates, reproduction is regulated by the brain-pituitary-gonadal axis (BPG-axis), and gonadotropin releasing hormone (GnRH) is one of its key components. Therefore, to better understand the physiology of reproduction in the turbot, three of the genes encoding GnRH subtypes—sbGnRH, cGnRH-II and sGnRH—were cloned and sequenced by isolating the cDNA sequences. The localizations and patterns of expression of their mRNAs were also evaluated during seasonal gonadal development. All three mRNAs were expressed abundantly in the brain; sbGnRH and sGnRH mRNAs were also detected in the gonads and pituitary gland, and sbGnRH expression was much higher than that of sGnRH, indicating the critical role of sbGnRH in regulating the BPG-axis. Moreover, the brain expression patterns of sbGnRH and sGnRH mRNAs showed an increased trend during gonadal development, peaking in mature stages. This indicated the direct regulation of gonadal development by the GnRH system. In addition, cGnRH-II mRNA expression showed no significant variations, suggesting that cGnRH-II is not critically involved in the control of reproduction. Further, the mRNA abundances of the three GnRH forms in the breeding season were significantly higher than those in immature and post-breeding stages in all analyzed brain areas. Therefore, we propose that sbGnRH is the most important hormone for the regulation of reproduction in turbot via the BPG-axis. These results will help in better understanding the reproductive endocrine mechanisms of turbots and lay the groundwork for additional studies aimed at comparing the reproductive physiology of wild individuals with those raised under artificial conditions.

  4. The Expression of Serum Antibodies against Gonadotropin-releasing Hormone (GnRH1, Progonadoliberin-2, Luteinizing Hormone (LH, and Related Receptors in Patients with Gastrointestinal Dysfunction or Diabetes Mellitus

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    Bodil Roth

    2014-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH 1 and 2 and luteinizing hormone (LH receptors have been described in the gastrointestinal tract. We have previously demonstrated antibodies in serum against GnRH1 in patients with gastrointestinal dysfunction and diabetes mellitus, and antibodies against GnRH receptor, LH, and LH receptor in patients with infertility. The aim of this study was to search for the expression of serum antibodies against GnRH1 with an improved enzyme-linked immune sorbent assay (ELISA, and antibodies against progonadoliberin-2, GnRH2, GnRH receptor, LH, and LH receptor with newly developed ELISAs, in patients with gastrointestinal dysfunction or diabetes mellitus. Healthy blood donors served as controls. Medical records were scrutinized. Our conclusion was that IgM antibodies against GnRH1, progonadoliberin-2, and/or GnRH receptors were more prevalent in patients with functional gastrointestinal disorders, gastrointestinal dysmotility, and/or diabetes mellitus, whereas IgG antibodies against these peptides, and LH- and LH receptor antibodies, were expressed in the same magnitude as in controls.

  5. Spatially Selective, Testosterone-Independent Remodeling of Dendrites in Gonadotropin-Releasing Hormone (GnRH) Neurons Prepubertally in Male Rats

    Science.gov (United States)

    Ybarra, Natividad; Hemond, Peter J.; O'Boyle, Michael P.

    2011-01-01

    Adult GnRH neurons exhibit a stereotypic morphology with a small soma, single axon, and single dendrite arising from the soma with little branching. The adult morphology of GnRH neurons in mice reflects an anatomical consolidation of dendrites over postnatal development. We examined this issue in rat GnRH neurons with biocytin filling in live hypothalamic slices from infant males, as adult littermates and in gonad-intact males, castrated males, and in males with one of three levels of testosterone (T) treatment. Somatic area and total dendritic length were significantly greater in infant males than in adults. Moreover, total numbers of dendrite branches were greater in infant males as compared with adults. The number of higher order branches and the lengths of higher order branches were also greater in infant males than in adults. Most interestingly, in adults a single dendrite arose from the somata, consistently at 180° from the axon. In contrast, prepubertal animals had an average of 2.2 ± 0.2 primary dendrites arising from somata (range, one to seven primary dendrites). Angles relative to the axon at which dendrites in prepubertal males emanated from GnRH somata were highly variable. Castration at 25 d of age and castration at 25 d of age with one of three levels of T treatment did not influence morphological parameters when GnRH neurons were examined between 40 d and 48 d of age. Thus, a spatially selective remodeling of primary dendrites and consolidation of distal GnRH dendritic arbors occurs during postnatal development and is largely independent of T. PMID:21343259

  6. GnRH antagonist rescue protocol combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial.

    Science.gov (United States)

    Fouda, Usama M; Sayed, Ahmed M; Elshaer, Hesham S; Hammad, Bahaa Eldin M; Shaban, Mona M; Elsetohy, Khaled A; Youssef, Mohamed A

    2016-05-17

    The aim of this study was to compare the efficacy of antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS. Two hundred and thirty six patients were randomized in a 1:1 ratio to the cabergoline group or the antagonist rescue combined with cabergoline group. Both groups received oral cabergoline (0.5 mg/day) for eight days beginning on the day of HCG administration. In the antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, GnRH agonist (triptorelin) was replaced with GnRH antagonist (cetrorelix acetate) and the dose of HP-uFSH was reduced to 75 IU/day. HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. The study was open label and the outcome assessors (laboratory staff and the doctor who performed oocyte retrieval) were blind to treatment allocation. The incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI, 0.129-0.906]. Four cycles were cancelled in the cabergoline group. There were no significant differences between the groups with respect to the number of retrieved oocytes, metaphase II oocytes, high quality embryos and fertilization rate. Moreover, the implantation and pregnancy rates were comparable between both groups. GnRH antagonist rescue protocol combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS. Clinical trial.gov ( NCT02461875 ).

  7. Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols.

    Science.gov (United States)

    Toftager, Mette; Sylvest, Randi; Schmidt, Lone; Bogstad, Jeanette; Løssl, Kristine; Prætorius, Lisbeth; Zedeler, Anne; Bryndorf, Thue; Pinborg, Anja

    2018-01-01

    To compare self-reported quality of life, psychosocial well-being, and physical well-being during assisted reproductive technology (ART) treatment in 1,023 women allocated to either a short GnRH antagonist or long GnRH agonist protocol. Secondary outcome of a prospective phase 4, open-label, randomized controlled trial. Four times during treatment a questionnaire on self-reported physical well-being was completed. Further, a questionnaire on self-reported quality of life and psychosocial well-being was completed at the day of hCG testing. Fertility clinics at university hospitals. Women referred for their first ART treatment were randomized in a 1:1 ratio and started standardized ART protocols. Gonadotropin-releasing hormone analogue; 528 women allocated to a short GnRH antagonist protocol and 495 women allocated to a long GnRH agonist protocol. Self-reported quality of life, psychosocial well-being, and physical well-being based on questionnaires developed for women receiving ART treatment. Baseline characteristics were similar, and response rates were 79.4% and 74.3% in the GnRH antagonist and GnRH agonist groups, respectively. Self-reported quality of life during ART treatment was rated similar and slightly below normal in both groups. However, women in the GnRH antagonist group felt less emotional (adjusted odds ratio [AOR] 0.69), less limited in their everyday life (AOR 0.74), experienced less unexpected crying (AOR 0.71), and rated quality of sleep better (AOR 1.55). Further, women receiving GnRH agonist treatment felt worse physically. Women in a short GnRH antagonist protocol rated psychosocial and physical well-being during first ART treatment better than did women in a long GnRH agonist protocol. However, the one item on self-reported general quality of life was rated similarly. NCT00756028. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. [EFECTOS NEUROENDOCRINOS DE INSULINA, IGF-I Y LEPTINA SOBRE LA SECRECIÓN DE HORMONA LIBERADORA DE GONADOTROPINAS (GnRH

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    Ana Maria Rosales-Torres

    2011-10-01

    Full Text Available El balance energético del individuo determina en gran medida su eficiencia reproductiva. Bajo condiciones de balance negativo de energía, en la mayoría de los mamíferos, hay una reducción en la síntesis de hormona liberadora de gonadotropinas (GnRH, lo cual disminuye la actividad del eje hipotálamo-hipófisis-gónadas. Cuando el balance energético es revertido, el hipotálamo puede monitorear este cambio y restablecer la secreción de GnRH. La Insulina, el Factor de Crecimiento similar a la Insulina I (IGF-I y Leptina parecen ser los principales mensajeros que informan al hipotálamo sobre el estado energético del animal puesto que las concentraciones periféricas de estas hormonas en situaciones energéticas negativas o positivas, se han asociado con los cambios en la secreción de GnRH. En la presente revisión se muestra como IGF-I actúa directamente sobre neuronas secretoras de GnRH, afectando su síntesis, en tanto que insulina y leptina actúan sobre neuronas en el núcleo arcuato, las cuales hacen sinapsis con neuronas GnRH en el área preóptica medial. Sobre neuronas productoras de neuropéptido Y (NPY insulina y leptina reducen su expresión y por lo tanto el efecto negativo del NPY sobre neuronas GnRH. En cambio insulina y leptina estimulan la síntesis de péptido similar a la galanina (GLAP y propiomelanocortina (POMC. Tanto GALP como los metabolitos de POMC (hormona estimulante de melanocitos principalmente incrementan la síntesis de GnRH. Finalmente, la leptina, incrementa la expresión de kispeptina en neuronas del núcleo ARC. Kispeptina por su parte también tiene un efecto positivo sobre la síntesis y secreción de GnRH.

  9. Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH neurons in an estrous cycle and endocannabinoid signaling dependent manner.

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    Imre Farkas

    Full Text Available The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+-imaging revealed a ghrelin-triggered increase of the Ca(2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10 µM suggesting direct action of ghrelin. Estradiol (1nM eliminated the ghrelin-evoked rise of Ca(2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40 nM-4 μM administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1 antagonist AM251 (1µM and the intracellularly applied DAG-lipase inhibitor THL (10 µM, indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

  10. Impact of GnRH agonist triggering and intensive luteal steroid support on live-birth rates and ovarian hyperstimulation syndrome

    DEFF Research Database (Denmark)

    Iliodromiti, Stamatina; Lan, Vuong Thi Ngoc; Tuong, Ho Manh

    2013-01-01

    Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory implanta......Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory...

  11. Computational solution of the velocity and wall shear stress distribution inside a left carotid artery under pulsatile flow conditions

    Science.gov (United States)

    Arslan, Nurullah; Turmuş, Hakan

    2014-08-01

    Stroke is still one of the leading causes for death after heart diseases and cancer in all over the world. Strokes happen because an artery that carries blood uphill from the heart to the head is clogged. Most of the time, as with heart attacks, the problem is atherosclerosis, hardening of the arteries, calcified buildup of fatty deposits on the vessel wall. In this study, the fluid dynamic simulations were done in a left carotid bifurcation under the pulsatile flow conditions computationally. Pulsatile flow waveform is given in the paper. In vivo geometry and boundary conditions were obtained from a patient who has stenosis located at external carotid artery (ECA) and internal carotid artery (ICA) of his common carotid artery (CCA). The location of critical flow fields such as low wall shear stress (WSS), stagnation regions and separation regions were detected near the highly stenosed region and at branching region.

  12. Cisto ovariano em vacas de leite: incidência, resposta à aplicação de GnRH e desempenho reprodutivo Ovarian cysts in lactating dairy cows: incidence, response to GnRH, and reproductive performance

    Directory of Open Access Journals (Sweden)

    R.M. Santos

    2009-06-01

    Full Text Available A incidência de cistos ovarianos, a resposta ao tratamento com GnRH e os efeitos da ocorrência de cisto no desempenho reprodutivo e na taxa de descarte foram determinados em vacas lactantes da raça Holandesa. Vacas lactantes (n=333 foram avaliadas semanalmente por ultrassonografia a partir da quarta semana pós-parto, visando à detecção de corpos lúteos (CL e de folículos ovarianos maiores que 10mm. Na sétima semana pós-parto, as vacas foram classificadas: em ciclando (n=248; presença de CL em um dos exames ultrassonográficos; em anestro (n=54; ausência de CL e de folículos >25mm e com cisto (n=31; ausência de CL e presença de estruturas >25mm, quando foram distribuídas em: grupo-controle (n=16; sem tratamento e grupo-tratamento (n=15; vacas que receberam uma aplicação de GnRH. A taxa de cura foi de 60,0% no grupo das vacas tratadas e de 87,5% no grupo-controle. As vacas com cistos apresentaram maior intervalo parto-primeira inseminação artificial (PThe incidence of ovarian cysts, response to GnRH treatment, and effects on reproductive performance and culling rate of Holstein cows were determined. Ovaries of lactating cows (n=333, were weekly monitored by ultrasound, beginning at fourth week postpartum, to determine the presence of corpus luteum (CL and follicles greater than 10mm. In the seventh week the cows were classified as cycling (n=248; presence of corpus luteum (CL in one of the ultrasound evaluations; anovulatory (n=54; absence of CL and follicles less than 25mm, and cystic (n=31; absence of CL and presence of structures greater than 25mm. The cysts cows were distributed in two groups in the seventh week: control group (n=16; without treatment and treatment group (n=15; cows received one GnRH injection. The recovery rate was 60.0% in treated cows and 87.5% in control cows. The cystic cows had longer average interval from parturition to first AI (P<0.05; 91.4±8.3 vs. 77.8±2.5, higher number of services per

  13. Pulsatile dry cupping in patients with osteoarthritis of the knee - a randomized controlled exploratory trial.

    Science.gov (United States)

    Teut, Michael; Kaiser, Stefan; Ortiz, Miriam; Roll, Stephanie; Binting, Sylvia; Willich, Stefan N; Brinkhaus, Benno

    2012-10-12

    Cupping is used in various traditional medicine forms to relieve pain in musculoskeletal diseases. The aim of this study was to investigate the effectiveness of cupping in relieving the symptoms of knee osteoarthritis (OA). In a two-group, randomized controlled exploratory pilot study patients with a clinically and radiological confirmed knee OA (Kellgren-Lawrence Grading Scale: 2-4) and a pain intensity > 40 mm on a 100 mm visual analogue scale (VAS) were included. 40 Patients were randomized to either 8 sessions of pulsatile dry cupping within 4 weeks or no intervention (control). Paracetamol was allowed on demand for both groups. Outcomes were the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, the pain intensity on a VAS (0 mm = no pain to 100 mm = maximum intensity) and Quality of Life (SF-36) 4 and 12 weeks after randomization. Use of Paracetamol was documented within the 4-week treatment period. Analyses were performed by analysis of covariance adjusting for the baseline value for each outcome. 21 patients were allocated to the cupping group (5 male; mean age 68 ± SD 7.2) and 19 to the control group (8 male; 69 ± 6.8). After 4 weeks the WOMAC global score improved significantly more in the cupping group with a mean of 27.7 (95% confidence interval 22.1; 33.3) compared to 42.2 (36.3; 48.1) in the control group (p = 0.001). After 12 weeks the WOMAC global score were still significantly different in favor for cupping (31.0 (24.9; 37.2) vs. 40.8 (34.4; 47.3) p = 0.032), however the WOMAC subscores for pain and stiffness were not significant anymore. Significantly better outcomes in the cupping group were also observed for pain intensity on VAS and for the SF-36 Physical Component Scale compared to the control group after 4 and 12 weeks. No significant difference was observed for the SF-36 Mental Component Scale and the total number of consumed Paracetamol tablets between both groups (mean 9

  14. Pulsatile dry cupping in patients with osteoarthritis of the knee – a randomized controlled exploratory trial

    Science.gov (United States)

    2012-01-01

    Introduction Cupping is used in various traditional medicine forms to relieve pain in musculoskeletal diseases. The aim of this study was to investigate the effectiveness of cupping in relieving the symptoms of knee osteoarthritis (OA). Methods In a two-group, randomized controlled exploratory pilot study patients with a clinically and radiological confirmed knee OA (Kellgren-Lawrence Grading Scale: 2-4) and a pain intensity > 40 mm on a 100 mm visual analogue scale (VAS) were included. 40 Patients were randomized to either 8 sessions of pulsatile dry cupping within 4 weeks or no intervention (control). Paracetamol was allowed on demand for both groups. Outcomes were the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, the pain intensity on a VAS (0 mm = no pain to 100 mm = maximum intensity) and Quality of Life (SF-36) 4 and 12 weeks after randomization. Use of Paracetamol was documented within the 4-week treatment period. Analyses were performed by analysis of covariance adjusting for the baseline value for each outcome. Results 21 patients were allocated to the cupping group (5 male; mean age 68 ± SD 7.2) and 19 to the control group (8 male; 69 ± 6.8). After 4 weeks the WOMAC global score improved significantly more in the cupping group with a mean of 27.7 (95% confidence interval 22.1; 33.3) compared to 42.2 (36.3; 48.1) in the control group (p = 0.001). After 12 weeks the WOMAC global score were still significantly different in favor for cupping (31.0 (24.9; 37.2) vs. 40.8 (34.4; 47.3) p = 0.032), however the WOMAC subscores for pain and stiffness were not significant anymore. Significantly better outcomes in the cupping group were also observed for pain intensity on VAS and for the SF-36 Physical Component Scale compared to the control group after 4 and 12 weeks. No significant difference was observed for the SF-36 Mental Component Scale and the total number of consumed Paracetamol tablets

  15. Mock circulation loop to investigate hemolysis in a pulsatile total artificial heart.

    Science.gov (United States)

    Gräf, Felix; Finocchiaro, Thomas; Laumen, Marco; Mager, Ilona; Steinseifer, Ulrich

    2015-05-01

    Hemocompatibility of blood pumps is a crucial parameter that has to be ensured prior to in vivo testing. In contrast to rotary blood pumps, a standard for testing a pulsatile total artificial heart (TAH) has not yet been established. Therefore, a new mock circulation loop was designed to investigate hemolysis in the left ventricle of the ReinHeart TAH. Its main features are a high hemocompatibility, physiological conditions, a low priming volume, and the conduction of blood through a closed tubing system. The mock circulation loop consists of a noninvasive pressure chamber, an aortic compliance chamber, and an atrium directly connected to the ventricle. As a control pump, the clinically approved Medos-HIA ventricular assist device (VAD) was used. The pumps were operated at 120 beats per minute with an aortic pressure of 120 to 80 mm Hg and a mean atrial pressure of 10 mm Hg, generating an output flow of about 5 L/min. Heparinized porcine blood was used. A series of six identical tests were performed. A test method was established that is comparable to ASTM F 1841, which is standard practice for the assessment of hemolysis in continuous-flow blood pumps. The average normalized index of hemolysis (NIH) values of the VAD and the ReinHeart TAH were 0.018 g/100 L and 0.03 g/100 L, respectively. The standard deviation of the NIH was 0.0033 for the VAD and 0.0034 for the TAH. Furthermore, a single test with a BPX-80 Bio-Pump was performed to verify that the hemolysis induced by the mock circulation loop was negligible. The performed tests showed a good reproducibility and statistical significance. The mock circulation loop and test protocol developed in this study are valid methods to investigate the hemolysis induced by a pulsatile blood pump. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  16. Pulsatile dry cupping in patients with osteoarthritis of the knee – a randomized controlled exploratory trial

    Directory of Open Access Journals (Sweden)

    Teut Michael

    2012-10-01

    Full Text Available Abstract Introduction Cupping is used in various traditional medicine forms to relieve pain in musculoskeletal diseases. The aim of this study was to investigate the effectiveness of cupping in relieving the symptoms of knee osteoarthritis (OA. Methods In a two-group, randomized controlled exploratory pilot study patients with a clinically and radiological confirmed knee OA (Kellgren-Lawrence Grading Scale: 2-4 and a pain intensity > 40 mm on a 100 mm visual analogue scale (VAS were included. 40 Patients were randomized to either 8 sessions of pulsatile dry cupping within 4 weeks or no intervention (control. Paracetamol was allowed on demand for both groups. Outcomes were the Western Ontario and McMaster Universities Osteoarthritis (WOMAC score, the pain intensity on a VAS (0 mm = no pain to 100 mm = maximum intensity and Quality of Life (SF-36 4 and 12 weeks after randomization. Use of Paracetamol was documented within the 4-week treatment period. Analyses were performed by analysis of covariance adjusting for the baseline value for each outcome. Results 21 patients were allocated to the cupping group (5 male; mean age 68 ± SD 7.2 and 19 to the control group (8 male; 69 ± 6.8. After 4 weeks the WOMAC global score improved significantly more in the cupping group with a mean of 27.7 (95% confidence interval 22.1; 33.3 compared to 42.2 (36.3; 48.1 in the control group (p = 0.001. After 12 weeks the WOMAC global score were still significantly different in favor for cupping (31.0 (24.9; 37.2 vs. 40.8 (34.4; 47.3 p = 0.032, however the WOMAC subscores for pain and stiffness were not significant anymore. Significantly better outcomes in the cupping group were also observed for pain intensity on VAS and for the SF-36 Physical Component Scale compared to the control group after 4 and 12 weeks. No significant difference was observed for the SF-36 Mental Component Scale and the total number of consumed

  17. Assessment of turbulence models for pulsatile flow inside a heart pump.

    Science.gov (United States)

    Al-Azawy, Mohammed G; Turan, A; Revell, A

    2016-02-01

    Computational fluid dynamics (CFD) is applied to study the unsteady flow inside a pulsatile pump left ventricular assist device, in order to assess the sensitivity to a range of commonly used turbulence models. Levels of strain and wall shear stress are directly relevant to the evaluation of risk from haemolysis and thrombosis, and thus understanding the sensitivity to these turbulence models is important in the assessment of uncertainty in CFD predictions. The study focuses on a positive displacement or pulsatile pump, and the CFD model includes valves and moving pusher plate. An unstructured dynamic layering method was employed to capture this cyclic motion, and valves were simulated in their fully open position to mimic the natural scenario, with in/outflow triggered at control planes away from the valves. Six turbulence models have been used, comprising three relevant to the low Reynolds number nature of this flow and three more intended to investigate different transport effects. In the first group, we consider the shear stress transport (SST) [Formula: see text] model in both its standard and transition-sensitive forms, and the 'laminar' model in which no turbulence model is used. In the second group, we compare the one equation Spalart-Almaras model, the standard two equation [Formula: see text] and the full Reynolds stress model (RSM). Following evaluation of spatial and temporal resolution requirements, results are compared with available experimental data. The model was operated at a systolic duration of 40% of the pumping cycle and a pumping rate of 86 BPM (beats per minute). Contrary to reasonable preconception, the 'transition' model, calibrated to incorporate additional physical modelling specifically for these flow conditions, was not noticeably superior to the standard form of the model. Indeed, observations of turbulent viscosity ratio reveal that the transition model initiates a premature increase of turbulence in this flow, when compared with

  18. The heritability of glaucoma-related traits corneal hysteresis, central corneal thickness, intraocular pressure, and choroidal blood flow pulsatility.

    Science.gov (United States)

    Freeman, Ellen E; Roy-Gagnon, Marie-Hélène; Descovich, Denise; Massé, Hugues; Lesk, Mark R

    2013-01-01

    The purpose of this work was to investigate the heritability of potential glaucoma endophenotypes. We estimated for the first time the heritability of the pulsatility of choroidal blood flow. We also sought to confirm the heritability of corneal hysteresis, central corneal thickness, and 3 ways of measuring intraocular pressure. Measurements were performed on 96 first-degree relatives recruited from Maisonneuve-Rosemont Hospital in Montreal. Corneal hysteresis was determined using the Reichert Ocular Response Analyser. Central corneal thickness was measured with an ultrasound pachymeter. Three measures of intraocular pressure were obtained: Goldmann-correlated and corneal compensated intraocular pressure using the Ocular Response Analyser, and Pascal intraocular pressure using the Pascal Dynamic Contour Tonometer. The pulsatility of choroidal blood velocity and flow were measured in the sub-foveolar choroid using single-point laser Doppler flowmetry (Oculix). We estimated heritability using maximum-likelihood variance components methods implemented in the SOLAR software. No significant heritability was detected for the pulsatility of choroidal blood flow or velocity. The Goldman-correlated, corneal compensated, and Pascal measures of intraocular pressure measures were all significantly heritable at 0.94, 0.79, and 0.53 after age and sex adjustment (p = 0.0003, p = 0.0023, p = 0.0239). Central corneal thickness was significantly heritable at 0.68 (p = 0.0078). Corneal hysteresis was highly heritable but the estimate was at the upper boundary of 1.00 preventing us from giving a precise estimate. Corneal hysteresis, central corneal thickness, and intraocular pressure are all heritable and may be suitable as glaucoma endophenotypes. The pulsatility of choroidal blood flow and blood velocity were not significantly heritable in this sample.

  19. The heritability of glaucoma-related traits corneal hysteresis, central corneal thickness, intraocular pressure, and choroidal blood flow pulsatility.

    Directory of Open Access Journals (Sweden)

    Ellen E Freeman

    Full Text Available PURPOSE: The purpose of this work was to investigate the heritability of potential glaucoma endophenotypes. We estimated for the first time the heritability of the pulsatility of choroidal blood flow. We also sought to confirm the heritability of corneal hysteresis, central corneal thickness, and 3 ways of measuring intraocular pressure. METHODS: Measurements were performed on 96 first-degree relatives recruited from Maisonneuve-Rosemont Hospital in Montreal. Corneal hysteresis was determined using the Reichert Ocular Response Analyser. Central corneal thickness was measured with an ultrasound pachymeter. Three measures of intraocular pressure were obtained: Goldmann-correlated and corneal compensated intraocular pressure using the Ocular Response Analyser, and Pascal intraocular pressure using the Pascal Dynamic Contour Tonometer. The pulsatility of choroidal blood velocity and flow were measured in the sub-foveolar choroid using single-point laser Doppler flowmetry (Oculix. We estimated heritability using maximum-likelihood variance components methods implemented in the SOLAR software. RESULTS: No significant heritability was detected for the pulsatility of choroidal blood flow or velocity. The Goldman-correlated, corneal compensated, and Pascal measures of intraocular pressure measures were all significantly heritable at 0.94, 0.79, and 0.53 after age and sex adjustment (p = 0.0003, p = 0.0023, p = 0.0239. Central corneal thickness was significantly heritable at 0.68 (p = 0.0078. Corneal hysteresis was highly heritable but the estimate was at the upper boundary of 1.00 preventing us from giving a precise estimate. CONCLUSION: Corneal hysteresis, central corneal thickness, and intraocular pressure are all heritable and may be suitable as glaucoma endophenotypes. The pulsatility of choroidal blood flow and blood velocity were not significantly heritable in this sample.

  20. The Heritability of Glaucoma-Related Traits Corneal Hysteresis, Central Corneal Thickness, Intraocular Pressure, and Choroidal Blood Flow Pulsatility

    OpenAIRE

    Ellen E Freeman; Marie-Hélène Roy-Gagnon; Denise Descovich; Hugues Massé; Lesk, Mark R.

    2013-01-01

    PURPOSE: The purpose of this work was to investigate the heritability of potential glaucoma endophenotypes. We estimated for the first time the heritability of the pulsatility of choroidal blood flow. We also sought to confirm the heritability of corneal hysteresis, central corneal thickness, and 3 ways of measuring intraocular pressure. METHODS: Measurements were performed on 96 first-degree relatives recruited from Maisonneuve-Rosemont Hospital in Montreal. Corneal hysteresis was determined...

  1. Multi-objective optimization of pulsatile ventricular assist device hemocompatibility based on neural networks and a genetic algorithm.

    Science.gov (United States)

    Xu, Zihao; Yang, Ming; Wang, Xianghui; Wang, Zhong

    2015-08-04

    Given the benefit of pulsatile blood flow for perfusion of coronary arteries and end organs, pulsatile ventricular assist devices (VADs) are still widely used as paracorporeal mechanical circulatory support devices in clinical applications. However, poor hemocompatibility limits the service period of the VADs. Most previous improvements on VAD hemocompatibility were conducted by trial-and-error CFD analysis, which does not easily arrive at the best solution. In this paper, a multi-objective optimization method integrating neural networks and NSGA-II (Non-dominated Sorted Genetic Algorithm-II) based on FSI simulation was developed and applied to a pulsatile VAD to optimize its hemocompatibility. First, the VAD blood chamber was parameterized with the principal geometrical parameters. Three hemocompatibility indices including hemolysis, platelet activation, and platelet deposition were chosen as goal functions. The neural networks were built to fit the nonlinear relationship between goal functions and geometrical parameters. Next, a multi-objective optimization algorithm (NSGA-II) was used to search out the Pareto optimal solutions in the built neural networks. Finally, the best compromise solution was selected from the Pareto optimal solutions by a fuzzy membership approach and validated by FSI simulation. The best compromise solution simultaneously possesses an acceptable hemolysis index, platelet activation index, and platelet deposition index, and the corresponding relative errors between the indices predicted by optimization algorithm and the one calculated by FSI simulations are all less than 5%. The results suggest that the proposed multi-objective optimization method has the potential for application in optimizing pulsatile VAD hemocompatibility, and may also be applied to other blood-wetted devices.

  2. Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells.

    Science.gov (United States)

    Baird, Michelle A; Billington, Neil; Wang, Aibing; Adelstein, Robert S; Sellers, James R; Fischer, Robert S; Waterman, Clare M

    2017-01-15

    The role of nonmuscle myosin 2 (NM2) pulsatile dynamics in generating contractile forces required for developmental morphogenesis has been characterized, but whether these pulsatile contractions are an intrinsic property of all actomyosin networks is not known. Here we used live-cell fluorescence imaging to show that transient, local assembly of NM2A "pulses" occurs in the cortical cytoskeleton of single adherent cells of mesenchymal, epithelial, and sarcoma origin, independent of developmental signaling cues and cell-cell or cell-ECM interactions. We show that pulses in the cortical cytoskeleton require Rho-associated kinase- or myosin light chain kinase (MLCK) activity, increases in cytosolic calcium, and NM2 ATPase activity. Surprisingly, we find that cortical cytoskeleton pulses specifically require the head domain of NM2A, as they do not occur with either NM2B or a 2B-head-2A-tail chimera. Our results thus suggest that pulsatile contractions in the cortical cytoskeleton are an intrinsic property of the NM2A motor that may mediate its role in homeostatic maintenance of tension in the cortical cytoskeleton of adherent cells. © 2017 Baird et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. Developmental exposure to ethinylestradiol affects reproductive physiology, the GnRH neuroendocrine network and behaviors in female mouse

    Directory of Open Access Journals (Sweden)

    Lyes eDerouiche

    2015-12-01

    Full Text Available During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2, the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR or pharmacological (PHARMACO doses (0.1 and 1 µg/kg (body weight/day respectively, from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs.

  4. [Orientation studies of ovulation release in mice to test gonadotropic preparations. 2. FSH, PMSG and Gn-RH activity].

    Science.gov (United States)

    Bergfeld, J; Fliess, F R

    1981-01-01

    The doses of FSH (follicle-stimulating hormone), PMSG (pregnant mare serum gonadotrophin), and gn-RH (gonadotrophin-releasing hormone) effective in terms of triggering ovulation were determined in a mouse ovulation test. Varying doses of the above preparations were subcutaneously injected, 48 hours after overstimulation by injection of 0.5 or 1.0 IU of PMSG. The animals were sacrificed for examination, after another 18-20 hours had passed. Roughly 50 per cent of all animals treated (threshold) in one and the same dosage group (n = 5) had ovulated in response to 0.02-0.1 IU of FSH per animal. The following FSH and PMSG dosages are recommended: 0.02, 0.04, 0.06, 0.08, and 0.1 IU of FSH, 0.6, 1.0, 1.4, 1.8, 2.2, 2.6, 3.0 IU of PMSG. When mouse ovulation tests were used in orientation studies, ovulation was regularly induced by Gn-RH doses per animal between 0.01 and 1.0 micrograms. Dosage spacings or increments should be specified with higher accuracy by further studies.

  5. Risk of recurrent menorrhagia after hydrothermoablation: role of GnRH analogues neoadjuvant treatment in long-term successful rate.

    Science.gov (United States)

    Litta, P; Saccardi, C; Tommasi, L; Di Giuseppe, J; Delli Carpini, G; Ciavattini, A

    2014-01-01

    To evaluate the long-term effectiveness of presurgical therapy with GnRH analogues in patients who underwenthydrothermal endometrial ablation (HTA) for menorrhagia and assess the relationship between sonographically measured myometrium thickness and pelvic pain. A prospective randomized control study comparing 15 women (Group A) with presurgical subcutaneous triptorelin depot injection before HTA with controls (Group B, n = 15). Inclusion criteria were: recurrent menorrhagia, uterus length < 12 cm, no previous hormonal therapy for at least six month, and family plan completed. Student's t test was applied, as appropriate, to compare continuous variables. Proportion were compared with chi-squared. After 12 months of follow-up, Group A showed a significantly lower (0% vs 20%; p = 0.03) failure rate after hydrothermoablation than the Group B and a generally higher successful rate at 24 and 48 months. The discomfort, evaluated with VAS, showed a mean value of 47.6 +/- 15.9 +/- SD); 96.7% of women reported a mild-moderate postoperative pain. No perioperative and late complications were recorded. Presurgical treatment with GnRH analogues seems to improve long-term efficacy of HTA. Perioperative pelvic pain seems to not be affected by myometrium thickness.

  6. Sustainable agriculture

    National Research Council Canada - National Science Library

    Lichtfouse, Eric

    2009-01-01

    ... : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 9 Part I CLIMATE CHANGE Soils and Sustainable Agriculture: A Review : : : : : : : : : : : : : : : : : : : : : : : : : : Rattan Lal 15 Soils and Food Sufficiency...

  7. Sustainable Marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    In this article, three different conceptions of sustainable marketing are discussed and compared. These different conceptions are referred to as social, green, and critical sustainable marketing. Social sustainable marketing follows the logic of demand-driven marketing management and places the

  8. Using flow feature to extract pulsatile blood flow from 4D flow MRI images

    Science.gov (United States)

    Wang, Zhiqiang; Zhao, Ye; Yu, Whitney; Chen, Xi; Lin, Chen; Kralik, Stephen F.; Hutchins, Gary D.

    2017-02-01

    4D flow MRI images make it possible to measure pulsatile blood flow inside deforming vessel, which is critical in accurate blood flow visualization, simulation, and evaluation. Such data has great potential to overcome problems in existing work, which usually does not reflect the dynamic nature of elastic vessels and blood flows in cardiac cycles. However, the 4D flow MRI data is often low-resolution and with strong noise. Due to these challenges, few efforts have been successfully conducted to extract dynamic blood flow fields and deforming artery over cardiac cycles, especially for small artery like carotid. In this paper, a robust flow feature, particularly the mean flow intensity is used to segment blood flow regions inside vessels from 4D flow MRI images in whole cardiac cycle. To estimate this flow feature more accurately, adaptive weights are added to the raw velocity vectors based on the noise strength of MRI imaging. Then, based on this feature, target arteries are tracked in at different time steps in a cardiac cycle. This method is applied to the clinical 4D flow MRI data in neck area. Dynamic vessel walls and blood flows are effectively generated in a cardiac cycle in the relatively small carotid arteries. Good image segmentation results on 2D slices are presented, together with the visualization of 3D arteries and blood flows. Evaluation of the method was performed by clinical doctors and by checking flow volume rates in the vertebral and carotid arteries.

  9. Dairy intake is associated with memory and pulsatility index in heart failure.

    Science.gov (United States)

    Garcia, Sarah; Calvo, Dayana; Spitznagel, Mary Beth; Sweet, Lawrence; Josephson, Richard; Hughes, Joel; Gunstad, John

    2015-04-01

    Past work shows an inconsistent relationship between dairy intake and cognition in healthy older adults. A cross-sectional design was conducted to examine dairy consumption, cognitive dysfunction, and cerebral blood flow in a sample of older adults with heart failure (HF) to clarify their association in this population at high risk for adverse neurocognitive outcomes. A total of 86 older adults with HF (70.39 ± 9.51 years; 33.1% female) underwent neuropsychological testing, transcranial Doppler (TCD) sonography to quantify cerebral blood flow. Dairy intake was quantified using a brief self-report questionnaire. Partial correlations between the dairy consumption questionnaire and neuropsychological tests were conducted adjusting for HF severity, age, and sex. Contrary to expectations, results showed greater dairy intake was associated with poorer memory (r = -0.21, p = 0.01) and higher pulsatility index in the medial cerebral artery (r = -0.17, p = 0.05). Results suggest that greater dairy intake was associated with poorer memory performance in older adults with HF. Several possible explanations for these findings exist, including the contribution of high-fat dairy to underlying physiological processes that promote vascular cognitive impairment. Prospective studies employing objective measures specific to high and low fat dairy are needed to clarify this possibility.

  10. Pulsatile versus oscillatory shear stress regulates NADPH oxidase subunit expression: implication for native LDL oxidation.

    Science.gov (United States)

    Hwang, Juliana; Ing, Michael H; Salazar, Adler; Lassègue, Bernard; Griendling, Kathy; Navab, Mohamad; Sevanian, Alex; Hsiai, Tzung K

    2003-12-12

    Shear stress regulates endothelial nitric oxide and superoxide (O2-*) production, implicating the role of NADPH oxidase activity. It is unknown whether shear stress regulates the sources of reactive species production, consequent low-density lipoprotein (LDL) modification, and initiation of inflammatory events. Bovine aortic endothelial cells (BAECs) in the presence of 50 microg/mL of native LDL were exposed to (1) pulsatile flow with a mean shear stress (tau(ave)) of 25 dyne/cm2 and (2) oscillating flow at tau(ave) of 0. After 4 hours, aliquots of culture medium were collected for high-performance liquid chromatography analyses of electronegative LDL species, described as LDL- and LDL2-. In response to oscillatory shear stress, gp91phox mRNA expression was upregulated by 2.9+/-0.3-fold, and its homologue, Nox4, by 3.9+/-0.9-fold (PBAEC binding (PBAEC binding. The flow-dependent LDL oxidation is determined in part by the NADPH oxidase activity. The formation of modified LDL via O2-* production may also affect the regulation of monocyte chemoattractant protein-1 expression and monocyte/BAEC binding.

  11. Numerical analysis of bypass model geometrical parameters influence on pulsatile blood flow

    Directory of Open Access Journals (Sweden)

    Jonášová A.

    2011-06-01

    Full Text Available The present study is focused on the analysis of pulsatile blood flow in complete idealized 3D bypass models in dependence on three main geometrical parameters (stenosis degree, junction angle and diameter ratio. Assuming the blood to be an incompressible Newtonian fluid, the non-linear system of Navier-Stokes equations is integrated in time by a fully implicit second-order accurate fractional-step method. The space discretization is performed with the help of the cell-centred finite volume method formulated for unstructured tetrahedral grids. In order to model a realistic coronary blood flow, a time-dependent flow rate taken from corresponding literature is considered. For the analysis of obtained numerical results, special emphasis is placed on their comparison in the form of velocity isolines at several selected cross-sections during systolic and diastolic phases. The remainder of this paper is devoted to discussion of walls shear stress distribution and its oscillatory character described by the oscillatory shear index with regard to areas prone to development of intimal hyperplasia or to thrombus formation.

  12. Measurement of pulsatile turbulent flow downstream of polyurethane heart valve prosthesis using particle image velocimetry

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.K.; Sung, J.Y. [Graduate School, Seoul National University, Seoul (Korea); Chang, J.K.; Min, B.G.; Yoo, J.Y. [Seoul National University, Seoul (Korea)

    1998-11-01

    In-vitro flow characteristics downstream of a polyurethane artificial heart valve under a pulsatile flow condition were investigated using Particle Image Velocimetry (PIV). With a triggering system and a time-delay circuit the velocity field downstream of the valve was evaluated in conjunction with the opening behavior of a flexible valve leaflet during a cardiac cycle.. Reynolds shear stress distribution was calculated from the velocity fields at a peak systolic phase. Direct measurements of the wall shear stress by hot-film anemometry (HFA) were compared with the PIV data. The possibilities of vascular complications, such as the thrombus formation and red blood cell damage, could be estimated from the overall view of the instantaneous velocity and stress fields obtained. A correlation between the flow pattern downstream of the valve and the corresponding opening posture of the polyurethane valve membrane gives useful data necessary for the improved design of the frame structure and leaflet geometry of the valve. (author). 11 refs., 8 figs., 5 tabs.

  13. Cerebral Pulsatility Index Is Elevated in Patients with Elevated Right Atrial Pressure.

    Science.gov (United States)

    Lahiri, Shouri; Schlick, Konrad H; Padrick, Matthew M; Rinsky, Brenda; Gonzalez, Nestor; Jones, Heather; Mayer, Stephan A; Lyden, Patrick D

    2018-01-01

    Extracerebral venous congestion can precipitate intracranial hypertension due to obstruction of cerebral blood outflow. Conditions that increase right atrial pressure, such as hypervolemia, are thought to increase resistance to jugular venous outflow and contribute to cerebro-venous congestion. Cerebral pulsatility index (CPI) is considered a surrogate marker of distal cerebrovascular resistance and is elevated with intracranial hypertension. Thus, we sought to test the hypothesis that elevated right atrial pressure is associated with increased CPI compared to normal right atrial pressure. We retrospectively reviewed 61 consecutive patients with subarachnoid hemorrhage. We calculated CPI from transcranial Doppler studies and correlated these with echocardiographic measures of right atrial pressure. CPIs were compared from patients with elevated and normal right atrial pressure. There was a significant difference between CPI obtained from all patients with elevated right atrial pressure compared to those with normal right atrial pressure (P right and left hemispheric CPI from patients with both elevated and normal right atrial pressure. Patients with elevated right atrial pressure had significantly higher CPI compared to patients with normal right atrial pressure. These findings suggest that cerebro-venous congestion due to impaired jugular venous outflow may increase distal cerebrovascular resistance as measured by CPI. Since elevated CPI is associated with poor outcome in numerous neurological conditions, future studies are needed to elucidate the significance of these results in other populations. Copyright © 2017 by the American Society of Neuroimaging.

  14. A Novel Pulsatile Bioreactor for Mechanical Stimulation of Tissue Engineered Cardiac Constructs

    Directory of Open Access Journals (Sweden)

    Günther Eissner

    2011-07-01

    Full Text Available After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro.

  15. Mathematical Modeling of Rotary Blood Pumps in a Pulsatile In Vitro Flow Environment.

    Science.gov (United States)

    Pirbodaghi, Tohid

    2017-08-01

    Nowadays, sacrificing animals to develop medical devices and receive regulatory approval has become more common, which increases ethical concerns. Although in vivo tests are necessary for development and evaluation of new devices, nonetheless, with appropriate in vitro setups and mathematical models, a part of the validation process can be performed using these models to reduce the number of sacrificed animals. The main aim of this study is to present a mathematical model simulating the hydrodynamic function of a rotary blood pump (RBP) in a pulsatile in vitro flow environment. This model relates the pressure head of the RBP to the flow rate, rotational speed, and time derivatives of flow rate and rotational speed. To identify the model parameters, an in vitro setup was constructed consisting of a piston pump, a compliance chamber, a throttle, a buffer reservoir, and the CentriMag RBP. A 40% glycerin-water mixture as a blood analog fluid and deionized water were used in the hydraulic circuit to investigate the effect of viscosity and density of the working fluid on the model parameters. First, model variables were physically measured and digitally acquired. Second, an identification algorithm based on regression analysis was used to derive the model parameters. Third, the completed model was validated with a totally different set of in vitro data. The model is usable for both mathematical simulations of the interaction between the pump and heart and indirect pressure measurement in a clinical context. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  16. [Pulsatile Fontan: transcatheter closure of patent pulmonary artery. Follow up mid-term].

    Science.gov (United States)

    Gamboa, Ricardo; Mollón, Francisco P; Ríos Méndez, Raúl E; Cayré, Raúl O; Cazzaniga, Mario; Arroyo, Graciela M; Gutiérrez, Diego F

    2008-01-01

    We report the percutaneous closure of the pulmonary artery with residual shunt in patients with Fontan type circuit. Patients aged 9 and 11 years, with SaO2 of 88 and 96%, respectively. One of them coursing with headaches and functional class II. Both patients with total cavopulmonary anastomosis and fenestrated extracardiac conduit and permeable pulmonary artery (pulsatile Fontan). An Amplatzer duct-occluder device was implanted in the pulmonary artery entering from the femoral vein. Follow-up by means of clinical examination, imaging, and catetherization was pursued. Case 1, patency fenestration, Qp/Qs: 0.7/1. Case 2, closed fenestration, Qp/Qs; 1.3/1. We obtained immediate occlusion with 6/4 and 8/6 devices, respectively; pressure recordings revealed modification of the arterial morphology to biphasic; pulmonary pressure dropped 2 mm Hg in the first patient, without alteration in the second case; no changes in SaO2 were registered. Time of fluoroscopy was 57 and 45 minutes, respectively. Follow-up was maintained for 2.8 and 2.3 years, respectively. In patient 1, headaches disappeared and the fenestration was occluded with an Amplatzer septal-occluder one year later, raising SaO2 to 96%; no complications occurred nor was recanalization of the pulmonary artery needed in either case. Percutaneous occlusion of patent pulmonary artery in patients with Fontan type circuit is a feasible and effective procedure, and avoids overload of the single ventricle.

  17. Mathematical modeling of CSF pulsatile hydrodynamics based on fluid-solid interaction.

    Science.gov (United States)

    Masoumi, Nafiseh; Bastani, Dariush; Najarian, Siamak; Ganji, Fariba; Farmanzad, Farhad; Seddighi, Amir Saeed

    2010-06-01

    Intracranial pressure (ICP) is derived from cerebral blood pressure and cerebrospinal fluid (CSF) circulatory dynamics and can be affected in the course of many diseases. Computer analysis of the ICP time pattern plays a crucial role in the diagnosis and treatment of those diseases. This study proposes the application of Linninger et al.'s [IEEE Trans. Biomed. Eng., vol. 52, no. 4, pp. 557-565, Apr. 2005] fluid-solid interaction model of CSF hydrodynamic in ventricular system based on our clinical data from a group of patients with brain parenchyma tumor. The clinical experiments include the arterial blood pressure (ABP), venous blood pressure, and ICP in the subarachnoid space (SAS). These data were used as inputs to the model that predicts the intracranial dynamic phenomena. In addition, the model has been modified by considering CSF pulsatile production rate as the major factor of CSF motion. The approximations of ventricle enlargement, CSF pressure distribution in the ventricular system and CSF velocity magnitude in the aqueduct and foramina were obtained in this study. The observation of reversal flow in the CSF flow pattern due to brain tissue compression is another finding in our investigation. Based on the experimental results, no existence of large transmural pressure differences were found in the brain system. The measured pressure drop in the ventricular system was less than 5 Pa. Moreover, the CSF flow pattern, ICP distribution, and velocity magnitude were in good agreement with the published models and CINE (phase-contrast magnetic resonance imaging) experiments, respectively.

  18. Shape optimization of pulsatile ventricular assist devices using FSI to minimize thrombotic risk

    Science.gov (United States)

    Long, C. C.; Marsden, A. L.; Bazilevs, Y.

    2014-10-01

    In this paper we perform shape optimization of a pediatric pulsatile ventricular assist device (PVAD). The device simulation is carried out using fluid-structure interaction (FSI) modeling techniques within a computational framework that combines FEM for fluid mechanics and isogeometric analysis for structural mechanics modeling. The PVAD FSI simulations are performed under realistic conditions (i.e., flow speeds, pressure levels, boundary conditions, etc.), and account for the interaction of air, blood, and a thin structural membrane separating the two fluid subdomains. The shape optimization study is designed to reduce thrombotic risk, a major clinical problem in PVADs. Thrombotic risk is quantified in terms of particle residence time in the device blood chamber. Methods to compute particle residence time in the context of moving spatial domains are presented in a companion paper published in the same issue (Comput Mech, doi: 10.1007/s00466-013-0931-y, 2013). The surrogate management framework, a derivative-free pattern search optimization method that relies on surrogates for increased efficiency, is employed in this work. For the optimization study shown here, particle residence time is used to define a suitable cost or objective function, while four adjustable design optimization parameters are used to define the device geometry. The FSI-based optimization framework is implemented in a parallel computing environment, and deployed with minimal user intervention. Using five SEARCH/ POLL steps the optimization scheme identifies a PVAD design with significantly better throughput efficiency than the original device.

  19. Pulsatile flow of blood and heat transfer with variable viscosity under magnetic and vibration environment

    Science.gov (United States)

    Shit, G. C.; Majee, Sreeparna

    2015-08-01

    Unsteady flow of blood and heat transfer characteristics in the neighborhood of an overlapping constricted artery have been investigated in the presence of magnetic field and whole body vibration. The laminar flow of blood is taken to be incompressible and Newtonian fluid with variable viscosity depending upon temperature with an aim to provide resemblance to the real situation in the physiological system. The unsteady flow mechanism in the constricted artery is subjected to a pulsatile pressure gradient arising from systematic functioning of the heart and from the periodic body acceleration. The numerical computation has been performed using finite difference method by developing Crank-Nicolson scheme. The results show that the volumetric flow rate, skin-friction and the rate of heat transfer at the wall are significantly altered in the downstream of the constricted region. The axial velocity profile, temperature and flow rate increases with increase in temperature dependent viscosity, while the opposite trend is observed in the case of skin-friction and flow impedance.

  20. Physicochemical Effects Enhance Surfactant Transport in Pulsatile Motion of a Semi-Infinite Bubble

    Science.gov (United States)

    Pillert, Jerina E.; Gaver, Donald P.

    2009-01-01

    Abstract In this study, we investigate the sorption of pulmonary surfactant (Infasurf, Ony, Buffalo, NY) occurring at the air-liquid interface of a semi-infinite finger of air as it oscillates and progresses along a small rigid tube (1mminner diameter) occluded with a surfactant-doped solution of concentrations C=0.1,0.05,or0.01mg/mL. This simple experimental model of pulmonary airway reopening is designed to examine how altering the fluid flow field may lower reopening pressures and lead to a reduction in airway wall damage that is associated with the mechanical ventilation of an obstructed pulmonary system in airways of the deep lung with depleted endogenous and little exogenous surfactant. We analyzed a range of pulsatile flow scenarios by varying the oscillation frequency (0≤f≤1Hz), the oscillation flow waveform, and the steady flow rate (Qsteady=0.1or0.01mL/min). These experimental studies indicate that a high frequency (1 Hz, amplitude = 5 mm), fast-forward oscillation waveform superimposed onto a fast steady flow (0.1mL/min) substantially reduces mean reopening pressures (31%) as a consequence of the modified flow field and the commensurate increase in surfactant transport and adsorption. This result suggests that imposing high frequency, low amplitude oscillations during airway reopening will help to diminish ventilator-induced lung injury. PMID:18849416

  1. Numerical Study of Turbulent Pulsatile Blood Flow through Stenosed Artery Using Fluid-Solid Interaction

    Directory of Open Access Journals (Sweden)

    Mehdi Jahangiri

    2015-01-01

    Full Text Available The turbulent pulsatile blood flow through stenosed arteries considering the elastic property of the wall is investigated numerically. During the numerical model validation both standard k-ε model and RNG K-ε model are used. Compared with the RNG K-ε model, the standard K-ε model shows better agreement with previous experimental results and is better able to show the reverse flow region. Also, compared with experimental data, the results show that, up to 70% stenosis, the flow is laminar and for 80% stenosis the flow becomes turbulent. Assuming laminar or turbulent flow and also rigid or elastic walls, the results are compared with each other. The investigation of time-averaged shear stress and the oscillatory shear index for 80% stenosis show that assuming laminar flow will cause more error than assuming a rigid wall. The results also show that, in turbulent flow compared with laminar flow, the importance of assuming a flexible artery wall is more than assuming a rigid artery wall.

  2. Sigmoid sinus cortical plate dehiscence induces pulsatile tinnitus through amplifying sigmoid sinus venous sound.

    Science.gov (United States)

    Tian, Shan; Wang, Lizhen; Yang, Jiemeng; Mao, Rui; Liu, Zhaohui; Fan, Yubo

    2017-02-08

    Sigmoid sinus cortical plate dehiscence (SSCPD) is common in pulsatile tinnitus (PT) patients, and is treated through SSCPD resurfacing surgery in clinic, but the bio-mechanism is not clear as so far. This study aimed to clarify the bio-mechanism of PT sensation induced by SSCPD, and quantify the relationship of cortical plate (CP) thickness and PT sensation intensity. It was hypothesized that SSCPD would induce PT through significantly amplifying sigmoid sinus (SS) venous sound in this study. Finite element (FE) analysis based on radiology data of typical patient was used to verify this hypothesis, and was validated with clinical reports. In cases with different CP thickness, FE simulations of SS venous sound generation and propagation procedure were performed, involving SS venous flow field, vibration response of tissue overlying dehiscence area (including SS vessel wall and CP) and sound propagation in temporal bone air cells. It was shown in results that SS venous sound at tympanic membrane was 56.9dB in SSCPD case and -45.2dB in intact CP case, and was inaudible in all thin CP cases. It was concluded that SSCPD would directly induce PT through significantly amplifying SS venous sound, and thin CP would not be the only pathophysiology of PT. This conclusion would provide a theoretical basis for the design of SSCPD resurfacing surgery for PT patients with SSCPD or thin CP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Injection-molded capsular device for oral pulsatile release: development of a novel mold.

    Science.gov (United States)

    Zema, Lucia; Loreti, Giulia; Macchi, Elena; Foppoli, Anastasia; Maroni, Alessandra; Gazzaniga, Andrea

    2013-02-01

    The development of a purposely devised mold and a newly set up injection molding (IM) manufacturing process was undertaken to prepare swellable/erodible hydroxypropyl cellulose-based capsular containers. When orally administered, such devices would be intended to achieve pulsatile and/or colonic time-dependent delivery of drugs. An in-depth evaluation of thermal, rheological, and mechanical characteristics of melt formulations/molded items made of the selected polymer (Klucel® LF) with increasing amounts of plasticizer (polyethylene glycol 1500, 5%-15% by weight) was preliminarily carried out. On the basis of the results obtained, a new mold was designed that allowed, through an automatic manufacturing cycle of 5 s duration, matching cap and body items to be prepared. These were subsequently filled and coupled to give a closed device of constant 600 μm thickness. As compared with previous IM systems having the same composition, such capsules showed improved closure mechanism, technological properties, especially in terms of reproducibility of the shell thickness, and release performance. Moreover, the ability of the capsular container to impart a constant lag phase before the liberation of the contents was demonstrated irrespective of the conveyed formulation. Copyright © 2012 Wiley Periodicals, Inc.

  4. On the Evolution of Pulsatile Flow Subject to a Transverse Impulse Body Force

    Science.gov (United States)

    di Labbio, Giuseppe; Keshavarz-Motamed, Zahra; Kadem, Lyes

    2014-11-01

    In the event of an unexpected abrupt traffic stop or car accident, automotive passengers will experience an abrupt body deceleration. This may lead to tearing or dissection of the aortic wall known as Blunt Traumatic Aortic Rupture (BTAR). BTAR is the second leading cause of death in automotive accidents and, although quite frequent, the mechanisms leading to BTAR are still not clearly identified, particularly the contribution of the flow field. As such, this work is intended to provide a fundamental framework for the investigation of the flow contribution to BTAR. In this fundamental study, pulsatile flow in a three-dimensional, straight pipe of circular cross-section is subjected to a unidirectional, transverse, impulse body force applied on a strictly bounded volume of fluid. These models were simulated using the Computational Fluid Dynamics (CFD) software FLUENT. The evolution of fluid field characteristics was investigated during and after the application of the force. The application of the force significantly modified the flow field. The force induces a transverse pressure gradient causing the development of secondary flow structures that dissipate the energy added by the acceleration. Once the force ceases to act, these structures are carried downstream and gradually dissipate their excess energy.

  5. Pulsatile Non-Newtonian Fluid Flows in a Model Aneurysm with Oscillating Wall

    Directory of Open Access Journals (Sweden)

    Sumaia Parveen Shupti

    2017-11-01

    Full Text Available This research presents a numerical simulation of an unsteady two-dimensional channel flow of Newtonian and some non-Newtonian fluids using the finite-volume method. The walls of the geometry oscillate sinusoidally with time. We have used the Cartesian curvilinear coordinates to handle complex geometries, i.e., arterial stents and bulges and the governing Navier–Stokes equations have been modified accordingly. Physiological pulsatile flow has been used at the inlet to characterize four different non-Newtonian models, i.e., the (i Carreau, (ii Cross, (iii Modified Casson, and (iv Quemada. We have presented the numerical results in terms of wall shear stress (WSS, pressure distribution as well as the streamlines and discussed the hemodynamic behaviors for laminar and laminar to turbulent transitional flow conditions. An increase of wall shear stress and a decrease in wall pressure are significantly observed at the stenosis throat for high Reynolds number and highly stenosed arteries. Likewise, the flow recirculation also increases if the narrowing level and the Reynolds number increases in the dilated region which eventually leads the stream to experience a transition to turbulence at Re = 750. The results for the fluid flow through an aneurysm just after a stenosis with oscillating wall are novel in the literature.

  6. Numerical investigation of flow parameters for solid rigid spheroidal particle in a pulsatile pipe flow

    Science.gov (United States)

    Varghese, Joffin; Jayakumar, J. S.

    2017-09-01

    Quantifying, forecasting and analysing the displacement rates of suspended particles are essential while discussing about blood flow analysis. Because blood is one of the major organs in the body, which enables transport phenomena, comprising of numerous blood cells. In order to model the blood flow, a flow domain was created and numerically simulated. Flow field velocity in the stream is solved utilizing Finite Volume Method utilizing FVM unstructured solver. In pulsatile flow, the effect of parameters such as average Reynolds number, tube radius, particle size and Womersley number are taken into account. In this study spheroidal particle trajectory in axial direction is simulated at different values of pulsating frequency including 1.2 Hz, 3.33 Hz and 4.00 Hz and various densities including 1005 kg/m3 and 1025 kg/m3 for the flow domain. The analysis accomplishes the interaction study of blood constituents for different flow situations which have applications in diagnosis and treatment of cardio vascular related diseases.

  7. Realization of a permanent implantable pulsatile impeller heart with magnetically suspended motor.

    Science.gov (United States)

    Qian, K X; Zheng, M

    1997-07-01

    A permanent impeller heart that could work for years was once an idea. However, now this idea is turning into reality through the use of the magnetically suspended motor. Recently, with our implantable pulsatile impeller pump, 3 left ventricular assisted calves survived for about 2 months (62, 54, and 46 days, respectively). The termination of the experiments was related to wear of the mechanical bearing, which resulted in vibration of the rotor and pump failure. All the experimental animals were in good condition prior to pump failure. It seemed as if the experiments could have lasted indefinitely if the bearing had not failed. All the hematological and biochemical data of the calves remained in normal or acceptable ranges; neither blood damage nor organ dysfunction of any animal was detected. During autopsy, no severe thrombus formation was found in the pump or vessels although a low dose of heparin (0.5-0.8 g/h) was given to increase the activated coagulation time (ACT) to 1.5-2.0 times its normal value. To solve the problem of bearing wear, a magnetically suspended motor was investigated and applied to the impeller pump. On the opposite sides of a disc connected to the rotor, 2 permanent magnet rings were embedded, one for driving and the other for axial suspension. Because both the driving and suspending coils with iron cores attract the disc, no radial bearing was needed. This newly devised impeller heart promises to have long-term and permanent applications.

  8. Computational Fluid Dynamics Analysis of Pulsatile Blood Flow Behavior in Modelled Stenosed Vessels with Different Severities

    Directory of Open Access Journals (Sweden)

    Mohsen Mehrabi

    2012-01-01

    Full Text Available This study focuses on the behavior of blood flow in the stenosed vessels. Blood is modelled as an incompressible non-Newtonian fluid which is based on the power law viscosity model. A numerical technique based on the finite difference method is developed to simulate the blood flow taking into account the transient periodic behaviour of the blood flow in cardiac cycles. Also, pulsatile blood flow in the stenosed vessel is based on the Womersley model, and fluid flow in the lumen region is governed by the continuity equation and the Navier-Stokes equations. In this study, the stenosis shape is cosine by using Tu and Devil model. Comparing the results obtained from three stenosed vessels with 30%, 50%, and 75% area severity, we find that higher percent-area severity of stenosis leads to higher extrapressure jumps and higher blood speeds around the stenosis site. Also, we observe that the size of the stenosis in stenosed vessels does influence the blood flow. A little change on the cross-sectional value makes vast change on the blood flow rate. This simulation helps the people working in the field of physiological fluid dynamics as well as the medical practitioners.

  9. Modulation of a pulsatile release drug delivery system using different swellable/rupturable materials.

    Science.gov (United States)

    El-Maradny, Hoda A

    2007-11-01

    Diclofenac sodium tablets consisting of core coated with two layers of swelling and rupturable coatings were prepared and evaluated as a pulsatile drug delivery system. Cores containing the drug were prepared by direct compression using microcrystalline cellulose and Ludipress as hydrophilic excipients with the ratio of 1:1. Cores were then coated sequentially with an inner swelling layer of different swellable materials; either Explotab, Croscarmellose sodium, or Starch RX 1500, and an outer rupturable layer of different levels of ethylcellulose. The effect of the nature of the swelling layer and the level of the rupturable coating on the lag time and the water uptake were investigated. Drug release rate studies were performed using USP paddle method. Results showed the dependence of the lag time and water uptake prior to tablet rupture on the nature of the swelling layer and the coating levels. Explotab showed a significant decrease in the lag time, followed by Croscarmellose sodium and finally by Starch RX 1500. Increasing the level of ethylcellulose coating retarded the diffusion of the release medium to the swelling layer and the rupture of the coat, thus prolonging the lag time.

  10. Deformation of a membrane in a pulsatile flow: implications in heart valve design

    Science.gov (United States)

    Hernandez, C.; Guzman, J. E. V.; Zenit, R.

    2011-11-01

    Current designs of heart valves prosthetics have serious disadvantages and health issues for patients who use them. For this reason, a new design that combines durability (mechanical valves) and biocompatibility (biological valves) has to be conceived. Natural valves have very complex geometry because their leaflets have two principal curvatures, one imposed by the holding ring and a second one imposed by the bending of the closing arrangement. The objective of this research is to study the effects of both curvatures on the performance of a leaflet. It is well known that the increase of the curvature results in a larger stiffness, which, in turn, reduces the deflection of a leaflet. We conducted a study to determine the effect of changing the curvature (in two directions) of a flexible membrane when exposed to a steady and pulsatile flows. A study of the flow field that results from this interaction is also conducted by PIV measurements. Preliminary results of the leaflet deflection for many stiffnesses, curvatures and flow conditions will be presented and discussed.

  11. Nonlinear dynamics of shells conveying pulsatile flow with pulse-wave propagation. Theory and numerical results for a single harmonic pulsation

    Science.gov (United States)

    Tubaldi, Eleonora; Amabili, Marco; Païdoussis, Michael P.

    2017-05-01

    In deformable shells conveying pulsatile flow, oscillatory pressure changes cause local movements of the fluid and deformation of the shell wall, which propagate downstream in the form of a wave. In biomechanics, it is the propagation of the pulse that determines the pressure gradient during the flow at every location of the arterial tree. In this study, a woven Dacron aortic prosthesis is modelled as an orthotropic circular cylindrical shell described by means of the Novozhilov nonlinear shell theory. Flexible boundary conditions are considered to simulate connection with the remaining tissue. Nonlinear vibrations of the shell conveying pulsatile flow and subjected to pulsatile pressure are investigated taking into account the effects of the pulse-wave propagation. For the first time in literature, coupled fluid-structure Lagrange equations of motion for a non-material volume with wave propagation in case of pulsatile flow are developed. The fluid is modeled as a Newtonian inviscid pulsatile flow and it is formulated using a hybrid model based on the linear potential flow theory and considering the unsteady viscous effects obtained from the unsteady time-averaged Navier-Stokes equations. Contributions of pressure and velocity propagation are also considered in the pressure drop along the shell and in the pulsatile frictional traction on the internal wall in the axial direction. A numerical bifurcation analysis employs a refined reduced order model to investigate the dynamic behavior of a pressurized Dacron aortic graft conveying blood flow. A pulsatile time-dependent blood flow model is considered by applying the first harmonic of the physiological waveforms of velocity and pressure during the heart beating period. Geometrically nonlinear vibration response to pulsatile flow and transmural pulsatile pressure, considering the propagation of pressure and velocity changes inside the shell, is here presented via frequency-response curves, time histories, bifurcation

  12. [Variation in pituitary responsiveness to synthetic gonadotropin releasing hormone (GnRH) during different phases of the menstrual cycle (author's transl)].

    Science.gov (United States)

    Rosemberg, E; Purohit, P; Takekida, H

    1974-01-01

    Synthetic GnRH, at a dose of 100 mcg, was injected intravenously into 12 healthy, single, regulary menstruating women in order to test the capacity of the pituitary to release LH and FSH in response to the administration of the decapeptide. A total of 12 tests was performed during different stages of the menstrual cycle, i.e., on D 3-4, D 13-16 and D 21-29 of the cycle. Following GnRH administration, there was a rapid increase in serum levels of LH. Although there was a pronounced variation of responses in the course of the menstrual cycle, the maximum response was observed 30 to 40 min., after injection. The mean net increases of LH (M +/- SE mIU/ml) were in the following order: 118 +/- 22 in the preovulatory phase, 63 +/- 12 in the midluteal phase, and 35 +/- 7 in the early follicular phase. A concomitant but much smaller rise in serum levels of FSH was observed. These data indicate that the sensitivity of pituitary gonadotrophs to GnRH is preferentially increased during the preovulatory phase of the cycle, thus lending further support to already published data which demonstrated increased pituitary sensitivity to GnRH toward midcycle.

  13. Simultaneous observation of the GnRH pulse generator activity and plasma concentrations of metabolites and insulin during fasting and subsequent refeeding periods in Shiba goats.

    Science.gov (United States)

    Matsuyama, Shuichi; Ohkura, Satoshi; Ichimaru, Toru; Sakurai, Katsuyasu; Tsukamura, Hiroko; Maeda, Kei-ichiro; Okamura, Hiroaki

    2004-12-01

    The time course of GnRH pulse generator activity and plasma concentrations of energy substrates and insulin were simultaneously observed in female goats during 4-day fasting and subsequent refeeding in the presence or absence of estrogen for a better understanding of the mechanism of energetic control of gonadotropin secretion in ruminants. The GnRH pulse generator activity was electrophysiologically assessed with the intervals of characteristic increases in multiple-unit activity (MUA volleys) in the mediobasal hypothalamus. In estradiol-treated ovariectomized (OVX+E2) goats, the MUA volley intervals increased as fasting progressed. Plasma concentrations of non-esterified fatty acid and ketone body increased, while those of acetic acid and insulin decreased during fasting. The MUA volley intervals and plasma concentrations of those metabolites and insulin were restored to pre-fasting levels after subsequent refeeding. In ovariectomized (OVX) goats, changes in plasma metabolites and insulin concentrations were similar to those in OVX+E2 goats, but the MUA volley intervals were not altered. The present results demonstrated that fasting suppressed GnRH pulse generator activity in an estrogen-dependent manner. Changes in plasma concentrations of energy substrates and insulin during fasting were associated with the GnRH pulse generator activity in the presence of estrogen, but not in the absence of the steroid in female goats.

  14. Adult height after spontaneous pubertal growth or GnRH analog treatment in girls with early puberty: a meta-analysis.

    Science.gov (United States)

    Bertelloni, Silvano; Massart, Francesco; Miccoli, Mario; Baroncelli, Giampiero I

    2017-06-01

    Early puberty (EP) has been defined as the onset of puberty in the low-normal range; it may be a cause for concern regarding a possible impairment of adult height (AH). This paper meta-analysed data on AH after spontaneous growth or after gonadotropin-releasing hormone (GnRH) analog treatment in girls with EP. A computerized literature search was conducted from 1980 to June 30, 2016. Only published studies in English were considered. Eight papers were selected (483 cases). In untreated girls (n = 300), predicted adult height (PAH) at start of follow-up (-0.559 SDS (95%CI -1.110 to 0.001); P = 0.050) was close to mid-parental height (MPH) (-0.557 SDS (95%CI -0.736 to -0.419); P puberty represents a main cause of consultation in paediatric endocrinology offices due to concerns of both practitioners and parents. • Treatment with GnRH analogs is sometimes attempted with the aim to improve adult height. What is New: • Untreated and GnRH analog treated girls with early puberty reached similar adult height. • Adult height was consistent with mid-parental height in both untreated and GnRH analog treated girls with early puberty.

  15. Longitudinal follow-up of bone density and body composition in children with precocious or early puberty before, during and after cessation of GnRH agonist therapy

    NARCIS (Netherlands)

    I.M. van der Sluis (Inge); A.M. Boot (Annemieke); E.P. Krenning (Eric); S.L.S. Drop (Stenvert); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    2002-01-01

    textabstractWe studied bone mineral density (BMD), bone metabolism, and body composition in 47 children with central precocious puberty (n = 36) or early puberty (n = 11) before, during, and after cessation of GnRH agonist. Bone density and body composition were measured with dual

  16. Pharmacokinetic/Pharmacodynamic Modelling of GnRH Antagonist Degarelix: A Comparison of the Non-linear Mixed-Effects Programs NONMEM and NLME

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Nielsen, Henrik Aalborg

    2004-01-01

    proposed by Lindstrom and Bates. The two programs were tested using clinical PK/PD data of a new gonadotropin-releasing hormone (GnRH) antagonist degarelix currently being developed for prostate cancer treatment. The pharmacokinetics of intravenous administered degarelix was analysed using a three...

  17. Supression of the steroid-primed luteinizing hormone surge in the female rat by sodium dimethyldithiocarbamate: Relationship to hypothalamic catecholamines and GnRH neuronal activation

    Science.gov (United States)

    In female rodents, hypothalamic norepinephrine (NE) has a role in stimulating the secretion of gonadotropin-releasing hormone (GnRH) that triggers the ovulatory surge of luteinizing hormone (LH). NE synthesis from dopamine requires the presence of dopamine--hydroxylase (DH) an...

  18. Single and repeated GnRH agonist stimulation tests compared with basal markers of ovarian reserve in the prediction of outcome in IVF

    NARCIS (Netherlands)

    Hendriks, D.J.; Broekmans, F.J.M.; Bancsi, L.F.J.M.M.; Looman, C.W.N.; Jong, F.H. de; Velde, E.R. te

    Purpose: To study the value of a single or repeated GnRH agonist stimulation test (GAST) in predicting outcome in IVF compared to basal ovarian reserve tests. Methods: A total of 57 women was included. In a cycle prior to the IVF treatment, on day 3, an antral follicle count (AFC) was performed

  19. Neuronal Gonadotrophin-Releasing Hormone (GnRH) and Astrocytic Gonadotrophin Inhibitory Hormone (GnIH) Immunoreactivity in the Adult Rat Hippocampus.

    Science.gov (United States)

    Ferris, J K; Tse, M T; Hamson, D K; Taves, M D; Ma, C; McGuire, N; Arckens, L; Bentley, G E; Galea, L A M; Floresco, S B; Soma, K K

    2015-10-01

    Gonadotrophin-releasing hormone (GnRH) and gonadotrophin inhibitory hormone (GnIH) are neuropeptides secreted by the hypothalamus that regulate reproduction. GnRH receptors are not only present in the anterior pituitary, but also are abundantly expressed in the hippocampus of rats, suggesting that GnRH regulates hippocampal function. GnIH inhibits pituitary gonadotrophin secretion and is also expressed in the hippocampus of a songbird; its role outside of the reproductive axis is not well established. In the present study, we employed immunohistochemistry to examine three forms of GnRH [mammalian GnRH-I (mGnRH-I), chicken GnRH-II (cGnRH-II) and lamprey GnRH-III (lGnRH-III)] and GnIH in the adult rat hippocampus. No mGnRH-I and cGnRH-II+ cell bodies were present in the hippocampus. Sparse mGnRH-I and cGnRH-II+ fibres were present within the CA1 and CA3 fields of the hippocampus, along the hippocampal fissure, and within the hilus of the dentate gyrus. No lGnRH-III was present in the rodent hippocampus. GnIH-immunoreactivity was present in the hippocampus in cell bodies that resembled astrocytes. Males had more GnIH+ cells in the hilus of the dentate gyrus than females. To confirm the GnIH+ cell body phenotype, we performed double-label immunofluorescence against GnIH, glial fibrillary acidic protein (GFAP) and NeuN. Immunofluorescence revealed that all GnIH+ cell bodies in the hippocampus also contained GFAP, a marker of astrocytes. Taken together, these data suggest that GnRH does not reach GnRH receptors in the rat hippocampus primarily via synaptic release. By contrast, GnIH might be synthesised locally in the rat hippocampus by astrocytes. These data shed light on the sites of action and possible functions of GnRH and GnIH outside of the hypothalamic-pituitary-gonadal axis. © 2015 British Society for Neuroendocrinology.

  20. GnRH agonist during luteal phase in women undergoing assisted reproductive techniques: systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Martins, W P; Ferriani, R A; Navarro, P A; Nastri, C O

    2016-02-01

    To identify, evaluate and summarize the available evidence regarding the effectiveness and safety of administering a gonadotropin releasing hormone (GnRH) agonist during the luteal phase in women undergoing assisted reproductive techniques. In this systematic review and meta-analysis, we searched for randomized controlled trials (RCTs) comparing the addition of a GnRH agonist during the luteal phase, compared with standard luteal-phase support. We searched seven electronic databases and hand-searched the reference lists of included studies and related reviews. Our primary outcome was live birth or ongoing pregnancy per randomized woman. Our secondary outcomes were clinical pregnancy per randomized woman, miscarriage per clinical pregnancy, adverse perinatal outcome and congenital malformations. The evidence from eight studies examining 2776 women showed a relative risk (RR) for live birth or ongoing pregnancy of 1.26 (95% CI, 1.04-1.53; I(2) = 58%). Sensitivity analysis when excluding the studies that did not report live birth and those at high risk of bias resulted in one study examining 181 women with an RR of 1.07 (95% CI, 0.73-1.58). Subgroup analysis separating the studies by single/multiple doses of GnRH agonists or by ovarian stimulation with GnRH agonist/antagonist was unable to explain the observed heterogeneity. The quality of the evidence was deemed to be very low: it was downgraded because of the limitation of the included studies, imprecision, inconsistency across the studies' results, and suspicion of publication bias. None of the included studies reported adverse perinatal outcomes or congenital malformations. There is evidence that adding GnRH agonist during the luteal phase improves the likelihood of ongoing pregnancy. However, this evidence is of very low quality and there is no evidence for adverse perinatal outcome and congenital malformations. We therefore believe that including this intervention in clinical practice would be premature

  1. A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients.

    Science.gov (United States)

    Rombauts, Luk; Healy, David; Norman, Rob J

    2006-01-01

    This randomized controlled trial was designed to assess the impact of oral contraceptive (OC) scheduling with a GnRH antagonist (ganirelix) regimen on the ovarian response of women undergoing recombinant FSH (rFSH) stimulation for IVF, compared with a non-scheduled ganirelix regimen and a long GnRH agonist (nafarelin) protocol. A total of 110 women was treated with an OC and ganirelix, 111 with ganirelix alone and 111 with nafarelin. The OC (containing 30 microg ethinylestradiol/150 microg desogestrel) was taken for 14-28 days and stopped 2 days prior to the start of rFSH treatment. Primary efficiency parameters were the number of cumulus-oocyte complexes (per attempt) and the number of grade 1 or 2 embryos (per attempt). In terms of follicular growth and hormone profiles, the OC-scheduled antagonist regimen mimicked the agonist regimen rather than the (non-scheduled) GnRH antagonist regimen. In the OC-scheduled GnRH antagonist group and the nafarelin group (versus the non-scheduled antagonist group), pituitary suppression was more profound at the start of stimulation (P growth (P < or = 0.001), longer stimulation was required (11.7 and 10.3 days respectively versus 9.4; P < or = 0.001), and more rFSH was used (2667 and 2222 IU versus 1966 IU; P < or = 0.001). In the three groups, the number of oocytes was similar (13.1, 12.9 and 11.5 respectively; not significant) as well as the number of good quality embryos (5.1, 5.7 and 5.0 respectively; not significant). OC treatment prior to the rFSH/ganirelix regimen can be successfully applied to schedule patients, although more days of stimulation and more rFSH are required than with a non-scheduled GnRH antagonist regimen.

  2. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

  3. Impedance cardiography: Pulsatile blood flow and the biophysical and electrodynamic basis for the stroke volume equations

    Directory of Open Access Journals (Sweden)

    Donald P Bernstein

    2010-01-01

    Full Text Available Impedance cardiography (ICG is a branch of bioimpedance pimarily concerned with the determination of left ventricular stroke volume (SV. As implemented, using the transthoracic approach, the technique involves applying a current field longitudinally across a segment of thorax by means of a constant magnitude, high frequency, low amplitude alternating current (AC. By Ohm's Law, the voltage difference measured within the current field is proportional to the electrical impedance Z (Ω. Without ventilatory or cardiac activity, Z is known as the transthoracic, static base impedance Z0. Upon ventricular ejection, a characteristic time dependent cardiac-synchronous pulsatile impedance change is obtained, ΔZ(t, which, when placed electrically in parallel with Z0, constitutes the time-variable total transthoracic impedance Z(t. ΔZ(t represents a dual-element composite waveform, which comprises both the radially-oriented volumetric expansion of and axially-directed forward blood flow within both great thoracic arteries. In its majority, however, ΔZ(t is known to primarily emanate from the ascending aorta. Conceptually, commonly implemented methods assume a volumetric origin for the peak systolic upslope of ΔZ(t, (i.e. dZ/dtmax, with the presumed units of Ω·s-1. A recently introduced method assumes the rapid ejection of forward flowing blood in earliest systole causes significant changes in the velocity-induced blood resistivity variation (Δρb(t, Ωcm·s-1, and it is the peak rate of change of the blood resistivity variation dρb(t/dtmax (Ωcm·s-2 that is the origin of dZ/dtmax. As a consequence of dZ/dtmax peaking in the time domain of peak aortic blood acceleration, dv/dtmax (cm·s-2, it is suggested that dZ/dtmax is an ohmic mean acceleration analog (Ω·s-2 and not a mean flow or velocity surrogate as generally assumed. As conceptualized, the normalized value, dZ/dtmax/Z0, is a dimensionless ohmic mean acceleration equivalent (s-2

  4. Computational sustainability

    CERN Document Server

    Kersting, Kristian; Morik, Katharina

    2016-01-01

    The book at hand gives an overview of the state of the art research in Computational Sustainability as well as case studies of different application scenarios. This covers topics such as renewable energy supply, energy storage and e-mobility, efficiency in data centers and networks, sustainable food and water supply, sustainable health, industrial production and quality, etc. The book describes computational methods and possible application scenarios.

  5. Gas exchange efficiency of an oxygenator with integrated pulsatile displacement blood pump for neonatal patients.

    Science.gov (United States)

    Schlanstein, Peter C; Borchardt, Ralf; Mager, Ilona; Schmitz-Rode, Thomas; Steinseifer, Ulrich; Arens, Jutta

    2014-01-01

    Oxygenators have been used in neonatal extracorporeal membrane oxygenation (ECMO) since the 1970s. The need to develop a more effective oxygenator for this patient cohort exists due to their size and blood volume limitations. This study sought to validate the next design iteration of a novel oxygenator for neonatal ECMO with an integrated pulsatile displacement pump, thereby superseding an additional blood pump. Pulsating blood flow within the oxygenator is generated by synchronized active air flow expansion and contraction of integrated silicone pump tubes and hose pinching valves located at the oxygenator inlet and outlet. The current redesign improved upon previous prototypes by optimizing silicone pump tube distribution within the oxygenator fiber bundle; introduction of an oval shaped inner fiber bundle core, and housing; and a higher fiber packing density, all of which in combination reduced the priming volume by about 50% (50 to 27 mL and 41 to 20 mL, respectively). Gas exchange efficiency was tested for two new oxygenators manufactured with different fiber materials: one with coating and one with smaller pore size, both capable of long-term use (OXYPLUS® and CELGARD®). Results demonstrated that the oxygen transfer for both oxygenators was 5.3-24.7 mlO2/min for blood flow ranges of 100-500 mlblood/min. Carbon dioxide transfer for both oxygenators was 3.7-26.3 mlCO2/min for the same blood flow range. These preliminary results validated the oxygenator redesign by demonstrating an increase in packing density and thus in gas transfer, an increase in pumping capacity and a reduction in priming volume.

  6. Dispersion phenomena of reactive solute in a pulsatile flow of three-layer liquids

    Science.gov (United States)

    Debnath, Sudip; Saha, Apu Kumar; Mazumder, B. S.; Roy, Ashis Kumar

    2017-09-01

    This study aims at investigating the dispersion process in an oscillatory flow of a layered liquid. The liquid is considered as a three-layer liquid where the center region is the Casson liquid surrounded by a Newtonian liquid layer flowing through a narrow pipe under the wall reaction. The perturbation technique has been used for solving the momentum equations. In order to assist the analysis of solute transport behavior, Aris-Barton's method of moments has been utilized, where different molecular diffusivities were assumed for different respective regions, yet to be constant. The effects of finite yield stress, viscosity ratio, density ratio, peripheral layer thickness, and irreversible absorption at the tube wall on dispersion are investigated in detail. In the cases of steady, unsteady, and combined flow situations, dispersion coefficient is found to be diminished by absorption parameter, viscosity ratio, and yield stress, respectively. In the case of a steady flow and unsteady convective diffusion of a reactive solute, dispersion coefficient is independent of density ratio. For both the unsteady and combined flows, density ratio provides a pulsatile behaviour of the dispersion process though an increase in the density ratio may faster the dispersion process. Dispersion at early times is not affected by absorption though a considerable effect is observed for large time. The presence of a peripheral layer enhances the value of the dispersion coefficient and is higher than the single layer Casson liquid flow. As strong as the non-Newtonian effect is considered, the dispersion process becomes slower. Larger values of molecular diffusivity at different layers are the reason for less dispersion coefficient. This study may be useful for understanding the dispersion process in the blood-like liquid flow analysis for microcirculation.

  7. Increased pulsatility index supports diagnosis of vascular parkinsonism versus idiopathic Parkinson's disease.

    Science.gov (United States)

    Caba, L M; Ferrairó, J I T; Torres, I M; Costa, J F V; Muñoz, R B; Martin, A L

    2017-12-29

    The diagnosis of vascular parkinsonism (VP) is based on a series of clinical criteria and neuroimaging findings. An increase in transcranial Doppler ultrasonography pulsatility index (PI) has been described as a frequent finding in patients with VP. We aimed to confirm this association and to determine the PI value with the highest sensitivity and specificity for diagnosis of VP. PI was determined in all patients admitted to Hospital Universitari i Politècnic La Fe due to parkinsonism between January 2012 and June 2016. We assessed the probability of having VP based on PI values in patients with a definite diagnosis of either VP or idiopathic Parkinson's disease (IPD). A ROC curve was created to determine the PI value with the highest sensitivity and specificity. We assessed a total of 146 patients with suspected parkinsonism; 54 (37%) were diagnosed with IPD and 15 (10%) with VP. Patients with VP were significantly older than those with IPD (mean age of 79 vs 68.5, P=.00144) and had a higher PI (median of 1.29 [IQR: 1.09-1.38] vs 0.96 [IQR: 0.89-1.16], P=.01328). In our sample, a PI of 1.09 conferred 84% sensitivity and 70% specificity. In our series, the PI was significantly higher in patients with VP than in those with IPD. We therefore support the use of transcranial Doppler ultrasonography for the initial assessment of elderly patients with akinetic-rigid syndrome. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Control of a Pediatric Pulsatile Ventricular Assist Device: A Hybrid Cardiovascular Model Study.

    Science.gov (United States)

    Ferrari, Gianfranco; Di Molfetta, Arianna; Zieliński, Krzysztof; Fresiello, Libera; Górczyńska, Krystyna; Pałko, Krzysztof Jakub; Darowski, Marek; Amodeo, Antonio; Kozarski, Maciej

    2017-12-01

    The aim of this work is to study pediatric pneumatic ventricle (PVAD) performance, versus VAD rate (VADR) and native heart rate (HR) ratio Rr (VADR/HR). The study uses a hybrid model of the cardiovascular system (HCS). HCS consists of a computational part (a lumped parameter model including left and right ventricles, systemic and pulmonary arterial and venous circulation) interfaced to a physical part. This permits the connection of a VAD (15 mL PVAD). Echocardiographic and hemodynamic data of a pediatric patient (average weight 14.3 kg, HR 100 bpm, systemic pressure 75/44 mm Hg, CO 1.5 L/min) assisted apically with asynchronous PVAD were used to set up a basal condition in the model. After model tuning, the assistance was started, setting VAD parameters (ejection and filling pressures, systole duration) to completely fill and empty the PVAD. The study was conducted with constant HR and variable VADR (50-120, step 10, bpm). Experiments were repeated for two additional patients' HRs, 90 and 110 bpm and for two values of systemic arterial resistance (Ras ) and Emax . Experimental data were collected and stored on disk. Analyzed data include average left and right ventricular volumes (LVV, RVV), left ventricular flow (LVF), VAD flow (VADF), and total cardiac output (COt). Data were analyzed versus Rr. LVV and RVV are sensitive to Rr and a left ventricular unloading corresponds in general to a right ventricular loading. In the case of asynchronous assistance, frequency beats are always present and the beat rate is equal to the difference between HR and VADR. In the case of pulsatile asynchronous LVAD assistance, VADR should be chosen to minimize frequency beat effects and right ventricular loading and to maximize left ventricular unloading. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  9. Pulsatility Index in Aortic Coarctation: A Possible Way to Evaluate Factors Affecting Stenting Outcome

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Keramati

    2012-03-01

    Full Text Available Background: The pulsatility index (PI shows continuous blood flow to the end organs and is a significant factor believed to decrease in aortic coarctation. Correction of this factor is of great importance in the treatment of stenotic lesions of the aorta. However, there are minimal data regarding the trend of changes in the PI after stent implantation. Furthermore, the association between the PI and other echocardiographic indices in patients undergoing stent implantation is unclear. This study was designed to evaluate changes in the PI following stenting and its correlation with other echocardiographic indices. Methods: Twenty-three patients with a diagnosis of aortic coarctation consecutively underwent two-dimensional and Doppler echocardiographic imaging modalities twice (before and after stenting. The patients were divided into two groups based on the percentage of increase in the PI after stenting ( < 50% or ≥ 50%. The relation between the post-stenting PI and the baseline echocardiographic indices was assessed. Results: The PI was increased from 0.89 (SD = 0.30 to 1.75 (SD = 0.51 after stenting (p value < 0.001. Baseline diastolic/systolic velocity (D/S velocity ratio of the abdominal aorta (p value = 0.013, mean velocity (p value = 0.033, and peak gradient of the descending aorta (p value = 0.033 were significantly higher in the patients with ≥ 50% increase in the PI after stenting. Conclusion: Our findings showed that elevation in the PI after stenting was a predictable criterion in patients with aortic coarctation: it was predicted by some baseline clinical and echocardiographic indices. Baseline D/S ratio velocity of the abdominal aorta, mean velocity and peak gradient of the descending aorta, and baseline systolic blood pressure were the statistically significant indices to predict ≥ 50% increase in the PI in our patients.

  10. Development of Press-Coated, Floating-Pulsatile Drug Delivery of Lisinopril

    Science.gov (United States)

    Jagdale, Swati C.; Suryawanshi, Vishnu M.; Pandya, Sudhir V.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

    2014-01-01

    Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations. PMID:24959410

  11. Simulation of a pulsatile total artificial heart: Development of a partitioned Fluid Structure Interaction model

    Science.gov (United States)

    Sonntag, Simon J.; Kaufmann, Tim A. S.; Büsen, Martin R.; Laumen, Marco; Linde, Torsten; Schmitz-Rode, Thomas; Steinseifer, Ulrich

    2013-04-01

    Heart disease is one of the leading causes of death in the world. Due to a shortage in donor organs artificial hearts can be a bridge to transplantation or even serve as a destination therapy for patients with terminal heart insufficiency. A pusher plate driven pulsatile membrane pump, the Total Artificial Heart (TAH) ReinHeart, is currently under development at the Institute of Applied Medical Engineering of RWTH Aachen University.This paper presents the methodology of a fully coupled three-dimensional time-dependent Fluid Structure Interaction (FSI) simulation of the TAH using a commercial partitioned block-Gauss-Seidel coupling package. Partitioned coupling of the incompressible fluid with the slender flexible membrane as well as a high fluid/structure density ratio of about unity led inherently to a deterioration of the stability (‘artificial added mass instability’). The objective was to conduct a stable simulation with high accuracy of the pumping process. In order to achieve stability, a combined resistance and pressure outlet boundary condition as well as the interface artificial compressibility method was applied. An analysis of the contact algorithm and turbulence condition is presented. Independence tests are performed for the structural and the fluid mesh, the time step size and the number of pulse cycles. Because of the large deformation of the fluid domain, a variable mesh stiffness depending on certain mesh properties was specified for the fluid elements. Adaptive remeshing was avoided. Different approaches for the mesh stiffness function are compared with respect to convergence, preservation of mesh topology and mesh quality. The resulting mesh aspect ratios, mesh expansion factors and mesh orthogonalities are evaluated in detail. The membrane motion and flow distribution of the coupled simulations are compared with a top-view recording and stereo Particle Image Velocimetry (PIV) measurements, respectively, of the actual pump.

  12. An original valveless artificial heart providing pulsatile flow tested in mock circulatory loops.

    Science.gov (United States)

    Tozzi, Piergiorgio; Maertens, Audrey; Emery, Jonathan; Joseph, Samuel; Kirsch, Matthias; Avellan, François

    2017-11-24

    We present the test bench results of a valveless total artificial heart that is potentially compatible with the pediatric population. The RollingHeart is a valveless volumetric pump generating pulsatile flow. It consists of a single spherical cavity divided into 4 chambers by 2 rotating disks. The combined rotations of both disks produce changes in the volumes of the 4 cavities (suction and ejection). The blood enters/exits the spherical cavity through 4 openings that are symmetrical to the fixed rotation axis of the first disk.Mock circulatory system: The device pumps a 37% glycerin solution through 2 parallel circuits, simulating the pulmonary and systemic circulations. Flow rates are acquired with a magnetic inductive flowmeter, while pressure sensors collect pressure in the left and right outflow and inflow tracts.In vitro test protocol: The pump is run at speeds ranging from 20 to 180 ejections per minute. The waveform of the pressure generated at the inflow and outflow of the 4 chambers and the flow rate in the systemic circulation are measured. At an ejection rate of 178 min-1, the RollingHeart pumps 5.3 L/min for a systemic maximal pressure gradient of 174 mmHg and a pulmonary maximal pressure gradient of 75 mmHg. The power input was 14 W, corresponding to an efficiency of 21%. The RollingHeart represents a new approach in the domain of total artificial heart. This preliminary study endorses the feasibility of a single valveless device acting as a total artificial heart.

  13. Geometry and fusion of aortic valves from pulsatile flow ventricular assist device patients.

    Science.gov (United States)

    May-Newman, Karen; Mendoza, Annamarie; Abulon, Dina J K; Joshi, Mrunalini; Kunda, Anand; Dembitsky, Walter

    2011-03-01

    Aortic valve commissural fusion is a process in which fibrous tissue is deposited at the aortic valve commissures, creating adhesion between leaflets and preventing opening. Fusion has recently been associated with the implantation of left ventricular assist devices (VADs), affecting upwards of 50% of patients in recent studies. Aortic incompetence has also been associated with pulsatile VAD use, but a specific structural mechanism has not been identified. The study aim was to measure aortic valve geometry and fusion in tissue samples from explanted hearts of VAD recipients and to identify features that might explain the development of aortic valve dysfunction. The diameter, perimeter and thickness of the aortic root, as well as the height, edge length and thickness of each of the three aortic leaflets were measured in seven valves. Histological studies were performed of both fused and unfused leaflets. The aortic root geometry showed an elliptical aorta, with asymmetric leaflets. The right coronary leaflet had the greatest edge length, but was thinnest. The other two leaflets were smaller, but slightly thicker. Overall, the aorta and valve geometry was within the normal range. Fusion was found in five of the seven valves studied, and often observed in multiple leaflets. Fusion length correlated loosely with the time of VAD support. Tissue from both fused and unfused valves showed unilateral fibrosis in the leaflets, and a loss of the laminar tissue structure that was related to the duration of VAD support. These findings support previous observations that pathological changes occur in the aortic valves of VAD patients shortly after implantation. While the tissue exhibits abnormalities in the structure, the geometry does not show gross remodeling such as annular dilatation or leaflet lengthening that might precede the development of aortic valve dysfunction. These changes are associated with the development of aortic valve fusion, and may be related to the

  14. Sigmoid sinus diverticulum and pulsatile tinnitus - Analysis of CT scans from 15 cases

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhaohui; Wang, Zhenchang; Xian, Junfang; Wang, Yongzhe; Liang, Xihong [Dept. of Radiology, Capital Medical Univ., Beijing Tongren Hospital, Beijing (China); Chen, Chengfang; Gong, Shusheng; Ma, Xiaobo; Li, Yi [Dept. of Otolaryngology Head and Neck Surgery, Capital Medical Univ., Beijing Tongren Hospital, Beijing (China)], e-mail: gongs@ccmu.edu.cn

    2013-09-15

    Background: Although the imaging features of sigmoid sinus diverticulum induced pulsatile tinnitus (PT) have been presented in some extent, detailed imaging findings still have not been systematically evaluated and precise diagnostic radiographic criteria has not been established. Purpose: To examine the computed tomography (CT) characteristics of sigmoid sinus diverticulum accompanied with PT. Material and Methods: Fifteen PT patients with sigmoid sinus diverticula proven by surgery were recruited after consenting. CT images of 15 patients were obtained and analyzed, including features of diverticula, brain venous systems, integrity of the sigmoid plate, and the degree of temporal bone pneumatization. Results: Sigmoid sinus diverticulum was located on the same side of PT in 15 patients. Diverticula originated at the superior curve of the sigmoid sinus in 11 patients and the descending segment of the sigmoid sinus in four patients. Sigmoid sinus diverticula focally eroded into the adjacent mastoid air cells in 12 patients and mastoid cortex in three patients. Among eight patients with unilateral dominant brain venous systems, the diverticula were seen on the dominant side in seven patients and non-dominant side in one patient. In contrast, the other seven patients showed co-dominant brain venous systems, with three presenting diverticula on the right side and four on the left. More notably, dehiscent sigmoid plate on the PT side was demonstrated in all patients. In addition, temporal bone hyper-pneumatization was found in nine patients, good and moderate pneumatization in three patients, respectively. Conclusion: Dehiscent sigmoid plate and extensive temporal bone pneumatization are two important imaging characteristics of the PT induced by sigmoid sinus diverticulum.

  15. A waterborne chemical cue from Gulf toadfish, Opsanus beta, prompts pulsatile urea excretion in conspecifics.

    Science.gov (United States)

    Fulton, Jeremy; LeMoine, Christophe M R; Bucking, Carol; Brix, Kevin V; Walsh, Patrick J; McDonald, M Danielle

    2017-03-15

    The Gulf toadfish (Opsanus beta) has a fully functional ornithine urea cycle (O-UC) that allows it to excrete nitrogenous waste in the form of urea. Interestingly, urea is excreted in a pulse across the gill that lasts 1-3h and occurs once or twice a day. Both the stress hormone, cortisol, and the neurotransmitter, serotonin (5-HT) are involved in the control of pulsatile urea excretion. This and other evidence suggests that urea pulsing may be linked to toadfish social behavior. The hypothesis of the present study was that toadfish urea pulses can be triggered by waterborne chemical cues from conspecifics. Our findings indicate that exposure to seawater that held a donor conspecific for up to 48h (pre-conditioned seawater; PC-SW) induced a urea pulse within 7h in naïve conspecifics compared to a pulse latency of 20h when exposed to seawater alone. Factors such as PC-SW intensity and donor body mass influenced the pulse latency response of naïve conspecifics. Fractionation and heat treatment of PC-SW to narrow possible signal candidates revealed that the active chemical was both water-soluble and heat-stable. Fish exposed to urea, cortisol or 5-HT in seawater did not have a pulse latency that was significantly different than seawater alone; however, ammonia, perhaps in the form of NH4Cl, was found to be a factor in the pulse latency response of toadfish to PC-SW and could be one component of a multi-component cue used for chemical communication in toadfish. Further studies are needed to fully identify the chemical cue as well as determine its adaptive significance in this marine teleost fish. Copyright © 2016. Published by Elsevier Inc.

  16. The Use of Fluid Mechanics to Predict Regions of Microscopic Thrombus Formation in Pulsatile VADs.

    Science.gov (United States)

    Topper, Stephen R; Navitsky, Michael A; Medvitz, Richard B; Paterson, Eric G; Siedlecki, Christopher A; Slattery, Margaret J; Deutsch, Steven; Rosenberg, Gerson; Manning, Keefe B

    2014-03-01

    We compare the velocity and shear obtained from particle image velocimetry (PIV) and computational fluid dynamics (CFD) in a pulsatile ventricular assist device (VAD) to further test our thrombus predictive methodology using microscopy data from an explanted VAD. To mimic physiological conditions in vitro, a mock circulatory loop is used with a blood analog that matched blood's viscoelastic behavior at 40% hematocrit. Under normal physiologic pressures and for a heart rate of 75 bpm, PIV data is acquired and wall shear maps are produced. The resolution of the PIV shear rate calculations are tested using the CFD and found to be in the same range. A bovine study, using a model of the 50 cc Penn State V-2 VAD, for 30 days at a constant beat rate of 75 beats per minute (bpm) provides the microscopic data whereby after the 30 days, the device is explanted and the sac surface analyzed using scanning electron microscopy (SEM) and, after immunofluorescent labeling for platelets and fibrin, confocal microscopy. Areas are examined based on PIV measurements and CFD, with special attention to low shear regions where platelet and fibrin deposition are most likely to occur. Data collected within the outlet port in a direction normal to the front wall of the VAD shows that some regions experience wall shear rates less than 500 s-1, which increases the likelihood of platelet and fibrin deposition. Despite only one animal study, correlations between PIV, CFD, and in vivo data show promise. Deposition probability is quantified by the thrombus susceptibility potential, a calculation to correlate low shear and time of shear with deposition.

  17. Pressure recovery in aortic stenosis: an in vitro study in a pulsatile flow model.

    Science.gov (United States)

    Voelker, W; Reul, H; Stelzer, T; Schmidt, A; Karsch, K R

    1992-12-01

    This study was designed to study pressure recovery in various models of aortic valve stenosis by performing hemodynamic measurements under physiologic conditions in a pulsatile aortic flow circuit. The results were used to validate calculations of pressure recovery based on theoretic considerations derived from fluid dynamics. Pressure recovery in aortic stenosis has not been systematically analyzed. Stenoses varying in size, shape (circular, Y-shaped, slitlike) and inlet configuration (sharp-edged, nozzle-shaped inlet, artificially stenosed bioprostheses) were used. Aortic pressures were measured at multiple sites distal to the stenotic orifice to determine pressure gradients and recovery. With decreasing orifice area (2, 1.5, 1 and 0.5 cm2) pressure recovery increased (5, 7, 10 and 16 mm Hg, respectively) and the index pressure recovery to maximal peak to peak gradient decreased (56%, 37%, 24% and 14%, respectively). For a given orifice size of 0.5 cm2, this index ranged between 12% for a Y-shaped orifice and 15% for a circular orifice with a nozzle (cardiac output 4 liters/min). Increasing the cardiac output increased pressure recovery, whereas the ratio of pressure recovery to maximal pressure gradient remained constant. The index pressure recovery to transvalvular pressure gradient, which expresses the hemodynamic relevance of pressure recovery, decreases with increasing severity of aortic stenosis but is independent of transvalvular flow. Thus, pressure recovery is of minor importance in severe aortic stenosis but may account for discrepancies between Doppler and manometric gradients observed in patients with mild to moderate aortic stenosis or a prosthetic valve in the aortic position.

  18. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  19. Amoxicillin pulsatile - MiddleBrook: APC 111, APC-111, PULSYS-enhanced amoxicillin.

    Science.gov (United States)

    2007-01-01

    MiddleBrook Pharmaceuticals (formerly Advancis Pharmaceutical) is developing an improved version of amoxicillin using its pulsatile oral drug delivery technology, called PULSYS. Amoxicillin PULSYS is intended to provide a lower treatment dose, once-daily alternative to currently approved amoxicillin and penicillin regimens for the treatment of adolescents/adults with pharyngitis and/or tonsillitis. If amoxicillin PULSYS is approved, it will be the first and only once-daily amoxicillin therapy approved for use in the US. Regulatory submissions for the treatment of pharyngitis/tonsillitis have been made in the US. Amoxicillin PULSYS is in clinical development for the treatment of pharyngitis and/or tonsillitis due to group A streptococcal infections in adolescents/adults as a tablet formulation. MiddleBrook was conducting clinical development of a sprinkle formulation for children. However, this has been put on hold for financial reasons. MiddleBrook is seeking regulatory approval for this product as a 505(b)(2) product, which is one that is not considered to be a completely new product, but is also not a generic product. It is a product with some differences from a previously approved product and clinical data to support such differences are required; however, the basic safety and efficacy studies may have been conducted by other organisations. In June 2007, Advancis Pharmaceutical was renamed as MiddleBrook Pharmaceuticals, Inc. MiddleBrook and Par Pharmaceuticals entered a co-promotion agreement for this product in June 2004. Par was to fund future development in exchange for co-exclusive marketing rights and exclusive rights to sell amoxicillin PULSYS. MiddleBrook retained responsibility for the manufacturing programme and also retained all patents and brand names and was responsible for their enforcement. However, this collaboration was subsequently terminated in August 2005 by Par Pharmaceutical. MiddleBrook received the US $4.75 million R&D reimbursement

  20. Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment

    DEFF Research Database (Denmark)

    Juul, A; Müller, J; Skakkebaek, N E

    1997-01-01

    In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific...... antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with Gn......RH agonists to evaluate the effect of normal and precocious puberty on PSA levels and to study the correlation between testosterone and PSA in boys....

  1. Serum inhibin A and inhibin B in central precocious puberty before and during treatment with GnRH agonists

    DEFF Research Database (Denmark)

    Sehested, A; Andersson, A M; Müller, J

    2000-01-01

    Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists...... both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation...... and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (...

  2. Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device

    Science.gov (United States)

    Gohean, Jeffrey R.; George, Mitchell J.; Pate, Thomas D.; Kurusz, Mark; Longoria, Raul G.; Smalling, Richard W.

    2012-01-01

    The purpose of this investigation is to utilize a computational model to compare a synchronized valveless pulsatile left ventricular assist device to continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous, pulsatile, valveless, dual piston positive displacement pump. These results were compared to measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared to the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device. PMID:23438771

  3. Endocrine archeology: do insects retain ancestrally inherited counterparts of the vertebrate releasing hormones GnRH, GHRH, TRH, and CRF?

    Science.gov (United States)

    De Loof, Arnold; Lindemans, Marleen; Liu, Feng; De Groef, Bert; Schoofs, Liliane

    2012-05-15

    Vertebrate releasing hormones include gonadotropin releasing hormone (GnRH), growth hormone releasing hormone (GHRH), corticotropin releasing hormone (CRF), and thyrotropin-releasing hormone (TRH). They are synthesized in the hypothalamus and stimulate the release of pituitary hormones. Here we review the knowledge on hormone releasing systems in the protostomian lineage. We address the question: do insects have peptides that may be phylogenetically related to an ancestral GnRH, GHRH, TRH, and CRF? Such endocrine archeology has become possible thanks to the growing list of fully sequenced genomes as well as to the continuously improving bioinformatic tool set. It has recently been shown that the ecdysozoan (nematodes and arthropods) adipokinetic hormones (AKHs), the lophotrochozoan (annelids and mollusks) GnRHs as well as the protochordate GnRHs are structurally related. The adipokinetic hormone precursor-related peptides (APRPs), in locusts encoded by the same gene that contains the AKH-coding region, have been forwarded as the structural counterpart of GHRH of vertebrates. CRF is relatively well conserved in insects, in which it functions as a diuretic hormone. Members of TRH-receptor family seem to have been conserved in some arthropods, but other elements of the thyroid hormone signaling system are not. A challenging idea is that in insects the functions of the thyroid hormones were taken over by juvenile hormone (JH). Our reconstruction suggests that, perhaps, the ancestral releasing hormone precursors played a role in controlling energy metabolism and water balance, and that releasing hormone functions as present in extant vertebrates were probably secondarily acquired. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Dominance of the forward compression wave in determining pulsatile components of blood pressure: similarities between inotropic stimulation and essential hypertension.

    Science.gov (United States)

    Fok, Henry; Guilcher, Antoine; Brett, Sally; Jiang, Benyu; Li, Ye; Epstein, Sally; Alastruey, Jordi; Clapp, Brian; Chowienczyk, Phil

    2014-11-01

    Pulsatile components of blood pressure may arise from forward (ventricular generated) or backward wave travel in the arterial tree. The objective of this study was to determine the relative contributions of forward and backward waves to pulsatility. We used wave intensity and wave separation analysis to determine pulsatile components of blood pressure during inotropic and vasopressor stimulation by dobutamine and norepinephrine in normotensive subjects and compared pulse pressure components in hypertensive (mean±SD, 48.8±11.3 years; 165±26.6/99±14.2 mm Hg) and normotensive subjects (52.2±12.6 years; 120±14.2/71±8.2 mm Hg). Dobutamine (7.5 μg/kg per minute) increased the forward compression wave generated by the ventricle and increased pulse pressure from 36.8±3.7 to 59.0±3.4 mm Hg (mean±SE) but had no significant effect on mean arterial pressure or the midsystolic backward compression wave. By contrast, norepinephrine (50 ng/kg per minute) had no significant effect on the forward compression wave but increased the midsystolic backward compression wave. Despite this increase in the backward compression wave, and an increase in mean arterial pressure, norepinephrine increased central pulse pressure less than dobutamine (increases of 22.1±3.8 and 7.2±2.8 mm Hg for dobutamine and norepinephrine, respectively; Phypertensive and normotensive subjects, respectively; Phypertensive and normotensive subjects. Increased central pulse pressure during inotropic stimulation and in essential hypertension results primarily from the forward compression wave. © 2014 American Heart Association, Inc.

  5. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...

  6. Sustaining dairy

    NARCIS (Netherlands)

    Villarreal Herrera, Georgina

    2017-01-01

    Dairy in Europe has undergone many changes in the last few years—the abolition of milk production quotas being a fundamental one. This study explores these changes in relation to the sustained social and environmental viability of the sector and how dairy processors' sustainability

  7. Sustainable Universities

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2011-01-01

    . Declarations tend to have impact on three trends. Firstly, there is emerging international consensus on the university’s role and function in relation to sustainable development; secondly, the emergence of national legislation, and thirdly, an emerging international competition to be leader in sustainable...... campus performance....

  8. Sustainable Transition

    DEFF Research Database (Denmark)

    Hansen, Ole Erik; Søndergård, Bent

    2014-01-01

    of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...

  9. Sustainable Learning

    Science.gov (United States)

    Cadwell, Louise; Dillon, Robert

    2011-01-01

    Green schools have moved into a new era that focuses on building a culture of sustainability in every aspect of learning in schools. In the early stages of sustainability education, the focus was on recycling and turning off the lights. Now, students and adults together are moving into the areas of advocacy and action that are based on a deep…

  10. Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes

    DEFF Research Database (Denmark)

    Aksglaede, L.; Jensen, Rikke Bodin Beck; Carlsen, E.

    2008-01-01

    testicular failure due to supernumerary X chromosomes. DESIGN: Cross-sectional study. METHODS: In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive...... basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary-gonadal axis has undergone...

  11. The pulsatility index and the resistive index in renal arteries. Associations with long-term progression in chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    1997-01-01

    The pulsatility index (PI) and the resistive index (RI) are used as pulsed-wave Doppler measurements of downstream renal artery resistance. PI and RI have been found to correlate with renal vascular resistance, filtration fraction and effective renal plasma flow in chronic renal failure. The aim...... of the present study was to evaluate the potential relationship between these indices and the rate of decline in renal function, as reflected by changes in different parameters of renal function in patients with chronic renal failure....

  12. The pulsatility index and the resistive index in renal arteries in patients with hypertension and chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Ladefoged, S D

    1995-01-01

    The pulsatility index (PI) and the resistive index (RI) are used as pulsed-wave Doppler measurement of downstream renal artery resistance. Little information is available on their value in chronic renal failure and their correlation to parameters of renal function and haemodynamics. The aim...... was to compare PI and RI of renal arteries in healthy volunteers and in patients with hypertension and chronic renal failure, and furthermore to study the correlation of these indices to measurements of renal haemodynamics and function by standard methods in patients with renal failure and hypertension....

  13. A multidisciplinary approach to sphenoid wing dysplasia presenting with pulsatile proptosis in neurofibromatosis Type 1: A rare case report

    Directory of Open Access Journals (Sweden)

    S Prathibha

    2018-01-01

    Full Text Available Neurofibromatosis (NF with sphenoid wing dysplasia is a rare clinical entity. Herewith, we present a case of NF with sphenoid wing dysplasia which presented with pulsatile progressive proptosis. Other ocular symptoms or visual disturbances were absent. Diagnosis of the condition was not easy and the management was a challenging task which needed multidisciplinary approach as there were ocular, neurological, orthopedic, and dermatological manifestations. With neurosurgical intervention, reconstruction of the sphenoid wing was possible. Proptosis was corrected without any disturbance of vision.

  14. Effect of GnRH analogue administration on Day 7 after natural mating on formation accessory corpus luteum, progesterone concentration and conception rate in llamas (Lama glama).

    Science.gov (United States)

    Abalos, Marcos C; Acuña, Francisco; Cancino, Andrea K; Aller, Juan F

    2018-03-01

    The objectives of the present study were to determine the effects of exogenous GnRH administered 7 days after breeding on the formation of an accessory corpus luteum (ACL), plasma progesterone (P 4 ) concentrations and pregnancy rates. Adult females (n = 71) having a follicle ≥ 7 mm in diameter in the ovary were naturally mated (Day 0). On Day 7, ultrasonic examination was performed to confirm the occurrence of ovulation as evidenced by presence of an induced corpus luteum (ICL). Females with an ICL plus a dominant follicle ≥ 7 mm (n = 56) were treated with saline solution (SS, n = 29) or GnRH analogue (n = 27). On Day 14, the formation of an ACL was observed by ultrasonography. Blood samples were collected on Days 7 and 14 to quantify plasma P 4 concentrations. On Day 14, 21 of 27 (77.8%) females in the GnRH group developed an ACL, whereas females in the SS group did not. Progesterone concentrations on Day 7 and 14 in those llamas diagnosed as pregnant on Day 30 were not different (P > 0.05) between groups. In addition, P 4 concentration was similar for GnRH-treated females having two CL to those with a single CL. Pregnancy rates were similar (P > 0.05) between SS and GnRH groups (55.2% compared with 74.1% respectively) and the pregnancy rate for the GnRH group was not affected (P > 0.05) by the number of CL observed at Day 14 (66.6% and 75.6% for females with one and two CL respectively). In conclusion, GnRH administration on Day 7 after breeding leads to ACL formation; however, neither the plasma P 4 concentration nor pregnancy rate was affected by having an ACL. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Numerical simulation of pulsatile flow with newtonian and non-newtonian behavior in arterial stenosis

    Directory of Open Access Journals (Sweden)

    MM Movahedi

    2008-03-01

    Full Text Available Background: There is considerable evidence that vascular fluid dynamics plays an important role in the developmentand prevalence of atherosclerosis which is one of the most widespread disease in humans .The onset and prevalence of atherosclerosis hemodynamic parameter are largely affected by geometric parameters. If any obstacle interferes with the blood flow, the above parameters change dramatically. Most of the arterial diseases, such as atherosclerosis, occur in the arteries with complex patterns of fluid flow where the blood dynamics plays an important role. Arterial stenosis mostly occurs in an area with a complex pattern of fluid flow, such as coronary artery, aorta bifurcation, carotid and vessels of lower limbs. During the past three decades, many experimental studies have been performed on the hemodynamic role of the blood in forming sediment in the inner wall of the vessels. It has been shown that forming sediment in the inner wall of vessels depends on the velocity of fluid and also on the amount of wall shear stress.Methods: We have examined the effect on the blood flow of local stenosis in carotid artery in numerical form using the incompressible Navier-Stockes equations. The profile of the velocity in different parts and times in the pulsatile cycle, separation and reattachment points on the wall, the distance stability of flow and also alteration caused by the wall shear stress in entire vessel were shown and compared with two behaviors flow (Newtonian and Non-Newtonian.Finally we describe the influence of the severity of the stenosis on the separation and reattachmentpoints for a Non-Newtonian fuid. Results: In the present study, we have pointed very low and high oscillating WSS (Wall Shear Stress values play a significant role in the development of forming sediment in the inner wall of vessels. Also, we obtain this probability is higher for Newtonian than Non-Newtonian fluid behavior.Conclusion: Based on our results, the

  16. Pulmonary artery pulsatility and effect on vessel diameter assessment in magnetic resonance imaging.

    Science.gov (United States)

    Shariat, Masoud; Schantz, Daryl; Yoo, Shi-Joon; Wintersperger, Bernd J; Seed, Mike; Alnafisi, Bahiyah; Chu, Leysia; Macgowan, Christopher K; van Amerom, Joshua; Grosse-Wortmann, Lars

    2014-02-01

    (pcine SSFP (p=0.44 for the TOF group and p=0.79 for ARVC group). Measurements on the MRA datasets were significantly larger than those on diastolic SSFP images (pcase. Cine SSFP images offer the additional advantage over the other methods in such that both the largest and the smallest diameter of the vessel during the cardiac cycle can be assessed using this technique. This is even more relevant in highly pulsatile circulations, such as patients with repaired TOF and significant pulmonary insufficiency. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Ovarian follicular responses to high doses of pulsatile luteinizing hormone in lactating dairy cattle.

    Science.gov (United States)

    Hampton, J H; Salfen, B E; Bader, J F; Keisler, D H; Garverick, H A

    2003-06-01

    Two experiments in lactating dairy cows examined ovarian follicular responses to high, frequent doses of exogenous LH pulses at levels associated with follicular cysts. In Experiment 1, estrus was synchronized in 12 cyclic lactating cows >40 d postpartum. Emergence of the second follicular wave (d 0) was determined by ultrasonography. Starting on d 1, cows received LH (40 microg/h; n = 7) or saline (2 mL/h; n = 5) in hourly pulses for up to 5 (n = 5) or 7 (n = 7) d. On d 2, all cows received two injections of PGF2alpha, 12 h apart. In experiment 2, 14 lactating cows (7 to 12 d postpartum) received LH (40 microg/h; n = 7) or saline (1 mL/h; n = 7) in hourly pulses for 7 d, beginning 24 h after start of the first follicular wave. Daily samples were used to determine serum concentrations of progesterone (P4), estradiol-17beta (E2), LH, and FSH. Profiles of LH were determined from blood samples collected at 12-min intervals for 8 h on d 3. During infusion of LH, serum P4 and FSH were similar across treatments in both experiments. Serum E2 concentrations were similar in experiment 1, but serum E2 was greater on d 2, 3, and 5 in LH-treated cows in experiment 2. Infusion increased LH pulse frequency and amplitude in both experiments. Formation of cysts did not differ between LH- and saline-treated cows in either experiment (1 of 7 vs. 0 of 5 and 1 of 6 vs. 0 of 7, respectively). Cows that ovulated had similar intervals to ovulation in experiment 1 [6.0 +/- 0.1 d (LH) vs. 6.4 +/- 0.2 d (saline)], but in experiment 2, ovulation was 14 d earlier in LH-treated cows (5.6 +/- 1.8 d vs 19.9 +/- 1.5 d). In conclusion, high concentrations of LH are not solely responsible for formation of cysts in lactating dairy cows. Pulsatile infusion of LH stimulated follicular growth and steroidogenesis and decreased time to first ovulation in anestrous postpartum cows.

  18. Reference ranges for uterine artery pulsatility index during the menstrual cycle: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Luís Guedes-Martins

    Full Text Available Cyclic endometrial neoangiogenesis contributes to changes in local vascular patterns and is amenable to non-invasive assessment with Doppler sonography. We hypothesize that the uterine artery (UtA impedance, measured by its pulsatility index (PI, exhibits a regular pattern during the normal menstrual cycle. Therefore, the main study objective was to derive normative new day-cycle-based reference ranges for the UtA-PI during the entire cycle from days 1 to 34 according to the isolated time effect and potential confounders such as age and parity.From January 2009 to December 2012, a cross-sectional study of 1,821 healthy women undergoing routine gynaecological ultrasound was performed. The Doppler flow of the right and left UtA-PI was studied transvaginally by colour and pulsed Doppler imaging. The mean right and left values and the presence or absence of a bilateral protodiastolic notch were recorded. Reference intervals for the PI according to the cycle day were generated by classical linear regression.The majority of patients (97.5% presented unilateral or bilateral UtA notches. The crude 5th, 50th, and 95th reference percentile curves of the UtA-PI at 1-34 days of the normal menstrual cycle were derived. In all curves, a progressive significant decrease occurred during the first 13 days, followed by an increase and recovery in the UtA-PI. The adjusted 5th, 50th, and 95th reference percentile curves for the effects of age and parity were also obtained. These two conditions generated an approximately identical UtA-PI pattern during the cycle, except with small but significant reductions at the temporal extremes.The median, 5th, and the 95th percentiles of the UtA-PI decrease during the first third of the menstrual cycle and recover to their initial values during the last two thirds of the cycle. The rates of decrease and recovery depend significantly on age and parity.

  19. The significance of vortex ring formation and nozzle exit over-pressure to pulsatile jet propulsion

    Science.gov (United States)

    Krueger, Paul Samuel

    Pulsatile jet propulsion can be accomplished using a fully-pulsed jet (i.e., a periodic series of starting jets or pulses), the unsteady nature of which engenders vortex ring formation. The propulsive significance of vortex ring formation in this setting is studied experimentally using a piston-cylinder mechanism to generate starting and fully-pulsed, round jets of water into water. Starting jets are considered separately since they are the limiting case of a fully-pulsed jet at zero pulsing frequency. Measurements of the total impulse per pulse (starting jets) and time-averaged thrust (fully-pulsed jets) are made using a force balance. Digital particle image velocimetry (DPIV) measurements provide information about the resulting jet flow. Piston stroke to diameter ratios (L/D) between 2 and 8 are used to generate the pulses for both types of jets. This range brackets the transition between pulses that generate isolated vortex rings (small L/D) and pulses that yield a leading vortex ring that has pinched off from the generating jet, producing a trailing jet (large L/D). Impulse measurements for the starting jets as a function of L/D indicate the leading vortex ring adds proportionately more impulse per pulse than a trailing jet. This leads to a maximum in the average thrust during a pulse at an L/D just before vortex ring pinch off is observed. The propulsive advantage of vortex ring formation over trailing-jet ejection is due to nozzle exit over-pressure. This over-pressure can be related to the acceleration of ambient fluid in the form of added and entrained mass during ring formation. A simple model is proposed to describe these effects at the initiation of an impulsive pulse. The thrust measurements for fully-pulsed jets show a propulsive benefit from vortex ring formation (i.e., non-dimensional thrust, FIJ , > 1) for all non-dimensional pulsing frequencies, StL, accessible by a fully-pulsed jet. As with starting jets (StL = 0), vortex ring pinch off reduces

  20. Differential effects of repeated restraint stress on pulsatile lutenizing hormone secretion in female Fischer, Lewis and Wistar rats.

    Science.gov (United States)

    Li, X F; Edward, J; Mitchell, J C; Shao, B; Bowes, J E; Coen, C W; Lightman, S L; O'Byrne, K T

    2004-07-01

    Stress activates the hypothalamic-pituitary-adrenocortical (HPA) axis and can suppress pulsatile luteinizing hormone (LH) secretion, resulting in reproductive dysfunction. The histocompatible inbred Fischer and Lewis rat strains exhibit marked phenotypic differences in the activity of the HPA axis, the former being more reactive. Using Fischer, Lewis and Wistar rats, we assessed effects of repeated restraint stress on pulsatile LH secretion. Adult rats were ovariectomized and fitted with cardiac catheters. Blood samples were collected at 5-min intervals for 3-5 h for detection of LH. Less frequent samples were collected for corticosterone measurement. After 2 h, rats were restrained for 60 min. The same regimen was repeated four times at 6-day intervals. The mean peak corticosterone levels achieved during the first restraint in Fischer rats were significantly higher than those in Lewis and Wistar rats. By the time of the fourth episode of restraint, there had been some adaptation of the corticosterone response in the Fischer, but not in the Lewis or Wistar rats. LH pulses were interrupted during the 1st restraint in all experimental groups, although only Fischer rats showed suppression of LH pulses during the subsequent 2-h postrestraint period. During the fourth restraint, LH pulse frequency was still reduced in Wistar, but not in Fischer and Lewis rats, both of which showed a complete habituation. These results suggest that differential control mechanisms underlie the response of the HPA and HPG axes to repeated restraint stress.

  1. Utilization of Pulsatile flow to Decellularize the Human Umbilical Arteries to Make Small-Caliber Blood Vessel Scaffolds.

    Science.gov (United States)

    Chen, Shengjie; Li, Jingxing; Dong, Peiqing

    2013-09-01

    To explore the effect of pulsatile flow in the decellularization process of small blood vessels. A total of 30 human umbilical cords were used in the current study. The umbilical cords were flushed with 0.25% trypsin/0.01% EDTA for 30 minutes, followed by treatment with 1% sodium dodecyl sulfate sodium dodecyl sulfate for 3 hours. The effectiveness of decellularization on the umbilical artery wall was analyzed by mechanical analysis. The scaffolds' biocompatibility was observed by co-culture with the human umbilical endothelial cells. The maximum stress of the arteries before and after denuding was 3.55 ± 0.42N and 3.50 ± 0.43N, respectively. Under the pressure of 300 mmHg, 28 pieces of umbilical cords remained intact before and after the flushing, while 2 pieces ruptured under 300 mmHg. There was no significant difference in mechanical properties between flushed and control arteries. Isolated human umbilical endothelial cells grow and spread well on the decellularized umbilical artery scaffolds. Decellularization by pulsatile flow in human umbilical artery is a convenient, rapid and efficient approach to increase the availability of small caliber blood vessel scaffolds. Decellularization; Human umbilical artery; Scaffolds; Small diameter blood vessel; Vascular tissue engineering.

  2. Changes in Bone Mineral Density and Metabolic Parameters after Pulsatile Gonadorelin Treatment in Young Men with Hypogonadotropic Hypogonadism

    Directory of Open Access Journals (Sweden)

    Chen-Xi Li

    2015-01-01

    Full Text Available To assess the prevalence of osteoporosis in young men with hypogonadotropic hypogonadism (HH and to investigate the changes of BMD and metabolic parameters, a total of 22 young male patients with HH and 20 healthy controls were enrolled in the study. BMD, biochemical, and hormonal parameters were measured in two groups. Osteoporosis was more prevalent in HH patients (45.45% than the control subjects (10.00% (P<0.001. The patients with HH had lower BMD in lumbar spine 2–4, femoral neck, and total hip (P<0.001, for all and higher fasting insulin (P=0.001, HOMA-IR (P=0.002, and SHBG (P<0.001 compared to the controls. After 6 months of pulsatile gonadorelin treatment, BMI (P=0.021 and BMD in lumbar spine 2–4, femoral neck, and total hip (P=0.002, P=0.003, and P=0.003, resp. increased dramatically and total cholesterol (P=0.034, fasting insulin (P=0.025, HOMA-IR (P=0.021, and SHBG (P=0.001 decreased significantly in HH patients. The study shows a higher prevalence of osteoporosis in young men with HH. Long-term pulsatile gonadorelin treatment indicates a positive effect on BMD and metabolic parameters of HH patients.

  3. Changes in intracranial venous blood flow and pulsatility in Alzheimer's disease: A 4D flow MRI study.

    Science.gov (United States)

    Rivera-Rivera, Leonardo A; Schubert, Tilman; Turski, Patrick; Johnson, Kevin M; Berman, Sara E; Rowley, Howard A; Carlsson, Cynthia M; Johnson, Sterling C; Wieben, Oliver

    2017-06-01

    Cerebral blood flow, arterial pulsation, and vasomotion may be important indicators of cerebrovascular health in aging and diseases of aging such as Alzheimer's disease. Noninvasive markers that assess these characteristics may be helpful in the study of co-occurrence of these diseases and potential additive and interacting effects. In this study, 4D flow MRI was used to measure intra-cranial flow features with cardiac-gated phase contrast MRI in cranial arteries and veins. Mean blood flow and pulsatility index as well as the transit time of the peak flow from the middle cerebral artery to the superior sagittal sinus were measured in a total of 104 subjects comprising of four groups: (a) subjects with Alzheimer's disease, (b) age-matched controls, (c) subjects with mild cognitive impairment, and (d) a group of late middle-aged with parental history of sporadic Alzheimer's disease. The Alzheimer's disease group exhibited: a significant decrease in mean blood flow in the superior sagittal sinus, transverse sinus, middle cerebral artery, and internal carotid arteries; a significant decrease of the peak and end diastolic blood flow in the middle cerebral artery and superior sagittal sinus; a faster transmission of peak flow from the middle cerebral artery to the superior sagittal sinus and increased pulsatility index along the carotid siphon.

  4. Hypothalamic effects of progesterone on regulation of the pulsatile and surge release of luteinising hormone in female rats.

    Science.gov (United States)

    He, Wen; Li, Xiaofeng; Adekunbi, Daniel; Liu, Yali; Long, Hui; Wang, Li; Lyu, Qifeng; Kuang, Yanping; O'Byrne, Kevin T

    2017-08-14

    Progesterone can block the oestradiol-induced GnRH/LH surge and inhibit LH pulse frequency. Recent studies reported that progesterone prevented premature LH surges during ovarian hyperstimulation in women. As the most potent stimulator of GnRH/LH release, kisspeptin is believed to mediate the positive and negative feedback effects of oestradiol in the hypothalamic anteroventral periventricular (AVPV) and arcuate (ARC) nuclei, while the region-specific role of progesterone receptors in these nuclei remains unknown. This study examined the hypothesis that progesterone inhibits LH surge and pulsatile secretion via its receptor in the ARC and/or AVPV nuclei. Adult female rats received a single injection of pregnant mare serum gonadotropin followed by progesterone or vehicle. Progesterone administration resulted in a significant prolongation of the oestrous cycle and blockade of LH surge. However, microinjection of the progesterone receptor antagonist, RU486, into the AVPV reversed the prolonged cycle length and rescued the progesterone blockade LH surge, while RU486 into the ARC shortened LH pulse interval in the progesterone treated rats. These results demonstrated that progesterone's inhibitory effect on the GnRH/LH surge and pulsatile secretion is mediated by its receptor in the kisspeptin enriched hypothalamic AVPV and ARC respectively, which are essential for progesterone regulation of oestrous cyclicity in rats.

  5. An Ultrasound Simulation Model for the Pulsatile Blood Flow Modulated by the Motion of Stenosed Vessel Wall.

    Science.gov (United States)

    Zhang, Qinghui; Zhang, Yufeng; Zhou, Yi; Zhang, Kun; Zhang, Kexin; Gao, Lian

    2016-01-01

    This paper presents an ultrasound simulation model for pulsatile blood flow, modulated by the motion of a stenosed vessel wall. It aims at generating more realistic ultrasonic signals to provide an environment for evaluating ultrasound signal processing and imaging and a framework for investigating the behaviors of blood flow field modulated by wall motion. This model takes into account fluid-structure interaction, blood pulsatility, stenosis of the vessel, and arterial wall movement caused by surrounding tissue's motion. The axial and radial velocity distributions of blood and the displacement of vessel wall are calculated by solving coupled Navier-Stokes and wall equations. With these obtained values, we made several different phantoms by treating blood and the vessel wall as a group of point scatterers. Then, ultrasound echoed signals from oscillating wall and blood in the axisymmetric stenotic-carotid arteries were computed by ultrasound simulation software, Field II. The results show better consistency with corresponding theoretical values and clinical data and reflect the influence of wall movement on the flow field. It can serve as an effective tool not only for investigating the behavior of blood flow field modulated by wall motion but also for quantitative or qualitative evaluation of new ultrasound imaging technology and estimation method of blood velocity.

  6. Dynamical systems characterization of inertial effects of fluid flow in a curved artery model under pulsatile flow forcing

    Science.gov (United States)

    Leggiero, Michael; Bulusu, Kartik V.; Plesniak, Michael W.

    2013-11-01

    The main objective of this study was to examine inertial effects in a 180-degree model of curved arteries under pulsatile inflow conditions. Two-component, two-dimensional particle image velocimetery (2C-2D PIV) data were acquired upstream of and at several cross-sectional locations in the curved artery model. A blood-analog fluid comprised of 71% saturated sodium iodide solution, 28% glycerol and 1% distilled water (by volume) was subjected to multi-harmonic pulsatile inflow functions. First, signal time-lag was quantified by cross-correlating the input (voltage-time) supplied to a programmable pump and the output PIV (flow rate-time) measurements. The experiment was then treated as a linear, time-invariant system, and frequency response was estimated for phase shifts across a certain spectrum. Input-output signal dissimilarities were attributable to intrinsic inertial effects of flow. By coupling pressure-time and upstream flow rate-time measurements, the experiment was modeled using system identification methods. Results elucidate the role of inertial effects in fluid flow velocity measurements and the effect of these delays on secondary flow structure detection in a curved artery model. Supported by the NSF Grant No. CBET- 0828903 and GW Center for Biomimetics and Bioinspired Engineering.

  7. Sustainable consumption

    DEFF Research Database (Denmark)

    Prothero, Andrea; Dobscha, Susan; Freund, Jim

    2011-01-01

    This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade our planet. Future research approaches to this interdisciplinary topic need to be comprehensive...... and systematic and will benefit from a variety of different perspectives. There are a number of opportunities for future research, and three areas are explored in detail. First, the essay considers the inconsistency between the attitudes and behaviors of consumers with respect to sustainability; next, the agenda...... is broadened to explore the role of individual citizens in society; and finally, a macro institutional approach to fostering sustainability is explored. Each of these areas is examined in detail and possible research avenues and public policy initiatives are considered within each of these separate...

  8. Stabilizing Sustainability

    DEFF Research Database (Denmark)

    Reitan Andersen, Kirsti

    The publication of the Brundtland Report in 1987 put the topic of sustainable development on the political and corporate agenda. Defining sustainable development as “a development that meets the needs of the future without compromising the ability of future generations to meet their own needs......” (WCED, 1987, p. 43), the Report also put a positive spin on the issue of sustainability by upholding capitalist beliefs in the possibility of infinite growth in a world of finite resources. While growth has delivered benefits, however, it has done so unequally and unsustainably. This thesis focuses...... on the textile and fashion industry, one of the world’s most polluting industries and an industry to some degree notorious for leading the ‘race to the bottom’ in global labour standards. Despite being faced with increasing demands to practise sustainability, most textile and fashion companies continue to fail...

  9. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  10. Sustainable Cities

    DEFF Research Database (Denmark)

    Georg, Susse; Garza de Linde, Gabriela Lucía

    Judging from the number of communities and cities striving or claiming to be sustainable and how often eco-development is invoked as the means for urban regeneration, it appears that sustainable and eco-development have become “the leading paradigm within urban development” (Whitehead 2003......), urban design competitions are understudied mechanisms for bringing about field level changes. Drawing on actor network theory, this paper examines how urban design competitions may bring about changes within the professional field through the use of intermediaries such as a sustainable planning....../assessment tool. The context for our study is urban regeneration in one Danish city, which had been suffering from industrial decline and which is currently investing in establishing a “sustainable city”. Based on this case study we explore how the insights and inspiration evoked in working with the tool...

  11. Sustainable responsibilities?

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    2015-01-01

    This working paper analyzes the conceptions of corporate responsibility for sustainable development in EU policies on CSR. The notion of corporate responsibility has until recently been limited to economical and legal responsibilities. Based on this narrow conception of corporate responsibility.......e. a combination of destruction and construction, this chapter will deconstruct conceptions of responsibility for sustainable development in these EU documents on CSR. A deconstructive conceptual analysis involves destructing dominant interpretations of a text and allowing for constructions of alternative...... such as sustainability actually means, but on what the concept says and does not say. A deconstructive analysis of EU policies on CSR, then, pinpoints that such policies are sites of conceptual struggles. This kind of analysis is suitable for studying conceptions of corporate responsibility for sustainable development...

  12. Agriculture: Sustainability

    Science.gov (United States)

    Sustainability creates and maintains the conditions under which humans and nature can exist in productive harmony, that permit fulfilling the food, feed, and fiber needs of our country and the social, economic and other requirements.

  13. Sustainable finance

    OpenAIRE

    Boersma-de Jong, Margreet F.

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence Sustainable Business Administration & Management Accounting, Financial Leadership and what is the importance of CSR in the financial sector

  14. Changes in bone mineral density and body composition in children with central precocious puberty and early puberty before and after one year of treatment with GnRH agonist.

    Science.gov (United States)

    Ko, Jung Hee; Lee, Hyo Sung; Lim, Jung Sub; Kim, Shin Mi; Hwang, Jin Soon

    2011-01-01

    Much concern has been raised and debated on the effects of obesity and bone mineral density (BMD) after treatment with GnRH agonist. The aim of this study was to assess BMD and body composition, especially percent body fat (%FM) based on dual-energy X-ray absorptiometry (DEXA), before and after 1 year of treatment with GnRH agonist in Korean girls. We assessed BMD and body composition in 121 Korean girls with precocious puberty before and after 1 year of treatment with GnRH agonist. BMD and body composition values were measured by using DEXA. The BMD standard deviation score of each region of interest for chronological age (CA) were higher than zero, but lower than zero for bone age (BA) at baseline and the gap was decreased after 1 year of GnRH agonist treatment. The fat mass (FM) and %FM for both CA and BA were significantly higher than zero at baseline. After GnRH agonist treatment, FM and %FM decreased for CA, but increased for BA. Pituitary-gonadal axis suppression by GnRH agonist does not reverse the progression of bone mass acquisition and does not increase the prevalence of obesity in Korean children with precocious puberty. Copyright © 2010 S. Karger AG, Basel.

  15. SUSTAINABLE TRANSPORTATION

    Directory of Open Access Journals (Sweden)

    Linda STEG

    2007-01-01

    Full Text Available This paper discusses possible contributions of psychologists to sustainable transportation. It is argued that in order to reach sustainable transportation, among others, behaviour changes of individual car users are needed. As transport policies will be more effective if they target important antecedents of travel behaviour, first, factors influencing such behaviour are discussed. It is argued that car use is very attractive and sometimes even necessary for many different reasons. This implies that a combination of policies is called for, each targeting different factors that support car use and hinder the use of more sustainable modes of transport. Next, the paper elaborates on policy strategies that may be employed to achieve sustainable transportation by changing car use. Increasing the attractiveness of sustainable transport modes by means of pull measures seems not sufficient to reduce the level of car use. Besides, car use should be made less attractive by means of push measures to force drivers to reconsider their travel behaviour. The acceptability of such policies may be increased by clearly communicating the aim of these policies, and the expected positive consequences (e.g., less congestion, improved environmental quality. Moreover, possible negative effects for individual freedom may be compensated by implementing additional policies aimed at facilitating the use of sustainable transport modes.

  16. Inducing puberty

    National Research Council Canada - National Science Library

    Delemarre, Eveline M; Felius, Bram; Delemarre-van de Waal, Henriette A

    2008-01-01

    ... (2008). Ferring Pharmaceuticals has supported the publication of these proceedings. Puberty is the result of increasing pulsatile secretion of the hypothalamic gonadotropin releasing hormone (GnRH...

  17. Comparison of a 'freeze-all' strategy including GnRH agonist trigger versus a 'fresh transfer' strategy including hCG trigger in assisted reproductive technology (ART)

    DEFF Research Database (Denmark)

    Stormlund, Sacha; Løssl, Kristine; Zedeler, Anne

    2017-01-01

    INTRODUCTION: Pregnancy rates after frozen embryo transfer (FET) have improved in recent years and are now approaching or even exceeding those obtained after fresh embryo transfer. This is partly due to improved laboratory techniques, but may also be caused by a more physiological hormonal......-all strategy with gonadotropin-releasing hormone (GnRH) agonist triggering versus human chorionic gonadotropin (hCG) trigger and fresh embryo transfer in a multicentre randomised controlled trial. METHODS AND ANALYSIS: Multicentre randomised, controlled, double-blinded trial of women undergoing assisted...... reproductive technology treatment including 424 normo-ovulatory women aged 18-39 years from Denmark and Sweden. Participants will be randomised (1:1) to either (1) GnRH agonist trigger and single vitrified-warmed blastocyst transfer in a subsequent hCG triggered natural menstrual cycle or (2) hCG trigger...

  18. Parity Differences in Heat Expression of Dairy Cows Synchronized with GnRH, CIDR and PGF2α during Dry Season in Zambia

    Directory of Open Access Journals (Sweden)

    E. S. Mwaanga*, K. Choongo, H. Simukoko and C. Chama1

    2012-01-01

    Full Text Available A study was conducted to investigate parity differences in heat expression of dairy cows heat-synchronized during the dry season when feed scarcity is common. Cyclic cows (n=65 aged 2 to 10 years with parity range of 0 to 7 were selected from small-holder dairy farms around Lusaka. Cows were divided into 3 groups of nulliparous, primiparous and pluriparous. Heat-was synchronized using gonadotrophin releasing hormone (GnRH and controlled intra-vaginal drug releasing device (CIDR. Heat detection was observed after CIDR withdraw. The study showed a significantly (P<0.05 lower number of primiparous cows (68% coming into heat compared to nulliparous (81.8% and pluriparous cows (83.3%. It was concluded that parity influences estrus expression rate in dairy cows following synchronization with GnRH, CIDR and PGF2α during the dry season in the sub-tropics.

  19. Administration of GnRH on the day of fixed-time artificial insemination (FTAI) and melengestrol acetate (MGA) administration after ftai in non-suckling nelore cattle

    OpenAIRE

    Silva, Rossane Pereira da; Instituto Federal de Educação; Leão, Karen Martins; Instituto Federal de Educação; Rodrigues, Moraima Castro; Instituto Federal de Educação; Marques, Thaisa Campos; Universidade Federal de Goiás, Escola de Veterinária; Silva, Natalia do Carmo; Universidade Federal de Goiás, Escola de Veterinária; Viu, Marco Antônio de Oliveira; Universidade Federal de Goiás

    2015-01-01

    Avaliou-se o efeito da aplicação de Acetato de Buserelina (GnRH) no momento da IATF e o efeito do fornecimento, via oral, de Acetato de Melengestrol (MGA) após IATF, sobre a taxa de concepção em vacas solteiras da raça Nelore. No Experimento I, avaliou-se o efeito da aplicação de GnRH no momento da IATF e do fornecimento de MGA do décimo terceiro ao décimo oitavo dia após a IATF (D24 ao D29 após o início do protocolo de IATF), em 215 vacas solteiras da raça Nelore divididas em quatro grupos e...

  20. Sustainable markets for sustainable energy

    Energy Technology Data Exchange (ETDEWEB)

    Millan, J.; Smyser, C.

    1997-12-01

    The author discusses how the Inter-American Development Bank (IDB) is involved in sustainable energy development. It presently has 50 loans and grants for non conventional renewable energy projects and ten grants for efficiency programs for $600 and $17 million respectively, representing 100 MW of power. The IDB is concerned with how to create a sustainable market for sustainable energy projects. The IDB is trying to work with government, private sector, NGOs, trading allies, credit sources, and regulators to find proper roles for such projects. He discusses how the IDB is working to expand its vision and objectives in renewable energy projects in Central and South America.

  1. Comparison between epidural injection of calcium–naloxone and intramuscular GnRH as therapeutic methods in the treatment of follicular ovarian cysts in dairy cattle

    OpenAIRE

    amirali kaveh; saeid Rezaye Haghdoust; samad mosaferi

    2014-01-01

    Ovarian cysts is one of the problems of dairy cattle with high production. The aim of this study was to evaluate the response to treatment of ovarian follicular cysts using calcium naloxone comparison with the conventional method of intramuscular GnRH injection. This study was conducted in third station dairy cattle farming center in Moghan on 54 cows' affected follicular ovarian cysts approximately 100 to 150 days after parturition. Following physical examination and diagnosis of the cystic ...

  2. Comparison of dual trigger with combination GnRH agonist and hCG versus hCG-only trigger of oocyte maturation for normal ovarian responders.

    Science.gov (United States)

    Zhou, Xingyu; Guo, Pingping; Chen, Xin; Ye, Desheng; Liu, Yudong; Chen, Shiling

    2018-02-01

    To investigate whether dual triggering of oocyte maturation with a gonadotropin-releasing hormone (GnRH) agonist and standard dose of human chorionic gonadotropin (hCG) can improve clinical outcomes for normal ovarian responders in GnRH antagonist cycles. The present retrospective cohort study included women aged up to 40 years with normal ovarian response who underwent in vitro fertilization and/or intracytoplasmic sperm injection under the GnRH antagonist protocol at Nanfang Hospital, China, between January 1 and December 31, 2015. Patients were grouped by whether oocyte maturation was triggered with GnRH agonist plus 5000-10 000 IU of hCG (dual trigger) or hCG alone. The primary outcome was live delivery rate. There were 325 women included; 224 in the dual trigger group and 101 in the hCG alone group. The live delivery rate did not differ significantly between the groups (P=0.083). The mean number of retrieved oocytes was similar in the two groups (P=0.719), but the mean number of two-pronuclear embryos (P=0.004), the number of embryos available (P=0.001), and the number of high-quality embryos (P=0.011) was higher in the dual trigger group. Dual trigger of oocyte maturation was not associated with any change in the live delivery rate but was associated with improvements in the quantity and quality of embryos; it could optimize pregnancy outcomes for normal ovarian responders. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. EFFECT OF POST-MATING GNRH TREATMET ON SERUM PROGESTERONE, LUTEINIZING HORMONE LEVELS, DURATION OF ESTROUS CYCLE AND PREGNANCY RATES IN COWS

    Directory of Open Access Journals (Sweden)

    H. YILDIZ, E. KAYGUSUZOĞLU, M. KAYA1 AND M. ÇENESIZ1

    2009-07-01

    Full Text Available Pregnancy rate, estrous cycle lenght, serum progesterone and luteinizing hormone (LH concentrations were determined in gonadotropin releasing hormone (GnRH; 10.5 μg synthetic gonadotrophin releasing hormone agonist, receptal administered cows on day 12 post-mating (n=9 compared to control cows (n=8. Their oestrous cycles were synchronised by intramuscular administration of prostaglandin F2 alpha (its analog, cloprostenol twice at 11 days interval. Estrous exhibited cows were mated naturally. Blood samples were collected every two days from all animals. Serum progesterone and LH concentrations were measured by ELISA method. GnRH administration significantly increased serum LH concentration which reached peak levels 2-3 h after treatment. However, serum progesterone concentration was not affected. There were no differences in mean progesterone concentrations on days 12 to 24 post-mating between GnRH administrated and control pregnant cows. However, in non pregnant animals, progesterone concentrations on days 16 in the treated group were lower than control group (P<0.01. Pregnancy diagnosis in animals made by B-mode ultrasonography between the 30th and 35th day showed that 77.7% of treated cows were pregnant compared to 50% in control group. Duration of the estrous cycle in the non-pregnant animals was not affected by the treatment (control, 21.3 ± 0.8 days; treated, 22.5 ± 0.5 days. In conclusion, this study supports the use of GnRH on day 12 post-mating as a method for enhancing pregnancy rates in lactating dairy cattle.

  4. Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study.

    Science.gov (United States)

    Huirne, Judith A F; van Loenen, Andre C D; Donnez, Jacques; Pirard, Céline; Homburg, Roy; Schats, Roel; McDonnell, Joseph; Lambalk, Cornelis B

    2006-08-01

    This randomized controlled study compared the effectiveness of a gonadotrophin releasing hormone (GnRH) antagonist protocol with or without oral contraceptive (OC) pretreatment on the number of oocytes retrieved in IVF or intracytoplasmic sperm injection (ICSI) patients. Sixty-four patients were randomized to start recombinant human FSH (r-hFSH) on day 2 or 3 after OC withdrawal (OC group) or on day 2 of a natural cycle (control group). From stimulation day 6 onwards, all patients were treated with daily (0.5 mg/ml) GnRH antagonist (Antide). OC pretreatment resulted in significantly lower starting concentrations of FSH, LH and oestradiol (P after OC pretreatment, leading to a significantly extended stimulation period (11.6 versus 8.7 days, P day of recombinant human chorionic gonadotrophin administration (15.4 versus 12.5, P = 0.02) and more oocytes retrieved (13.5 versus 10.2, P < 0.001) as compared with the control group. GnRH antagonist regimen, pretreated with OC, prevented the early endogenous FSH rise and improved follicular homogeneity, resulting in more oocytes. As a consequence of the extended treatment period, more rhFSH was required.

  5. Ovulation and conception rates according intravaginal progesterone device and hCG or GnRH to induce ovulation in buffalo during the off breeding season

    Directory of Open Access Journals (Sweden)

    P.S. Baruselli

    2010-02-01

    Full Text Available The objective of this study was to evaluate the effect of intravaginal progesterone device (P4; first or second use of different ovulatory inductors on ovulation and conception rates in buffaloes during the off breeding season. Two hundred and forty two buffaloes were allocated in four groups and received P4 device of first or second use plus estradiol benzoate on Day 0 (D0. The P4 device was removed and a dose of PGF2α and eCG was administered on D9. On D11, buffaloes received hCG or GnRH and 16hs after the animals were inseminated. The ultrasound examination was performed on D0 to verify the ovarian status, from D9 to D14 to establish the moment of ovulation and on D40 for pregnancy diagnosis. Data were analyzed by ANOVA and Chi-square test. There was no effect of interaction. The ovulation and conception rate were similar for P4 device of first and second use, for hCG and GnRH. Results indicate that the use of P4 device for two times and the use of GnRH instead of hCG provide satisfactory ovulation and conception rate in buffalo during the off breeding season and might reduce the cost of the protocol for artificial insemination.

  6. Comparison between epidural injection of calcium–naloxone and intramuscular GnRH as therapeutic methods in the treatment of follicular ovarian cysts in dairy cattle

    Directory of Open Access Journals (Sweden)

    amirali kaveh

    2014-08-01

    Full Text Available Ovarian cysts is one of the problems of dairy cattle with high production. The aim of this study was to evaluate the response to treatment of ovarian follicular cysts using calcium naloxone comparison with the conventional method of intramuscular GnRH injection. This study was conducted in third station dairy cattle farming center in Moghan on 54 cows' affected follicular ovarian cysts approximately 100 to 150 days after parturition. Following physical examination and diagnosis of the cystic cows, the animals were divided into three groups. The first group was the control group (5ml GnRH IM, the second group was the treatment group 1 (Nx via epidural injection 2 times with 3 day intervals and the third group was the treatment group 2 (Ca–Nx via epidural injection 2 times with 3 day intervals and 5 ml of intramuscular GnRH simultaneously with the second Ca-Nx injection. To check the results, the animals was examined two weeks after the last injection. The results indicated that there was a significant difference in luteinization rate between the first and second groups with more luteinization rate in the first group. There was no significant difference between the first and third group in luteinization rate. Also, there was a significant difference in luteinization rate between the second and third group, with more luteinization rate observed in the third group. There was no significant difference between the fertility rate of the treatment and control groups.

  7. Prevention of ovarian hyperstimulation syndrome in GnRH agonist IVF cycles in moderate risk patients: randomized study comparing hydroxyethyl starch versus cabergoline and hydroxyethyl starch.

    Science.gov (United States)

    Matorras, Roberto; Andrés, Maider; Mendoza, Rosario; Prieto, Begoña; Pijoan, Jose Ignacio; Expósito, Antonia

    2013-10-01

    To assess whether, in GnRH agonist IVF cycles where there is a risk of ovarian hyperstimulation syndrome (OHSS), the addition of cabergoline to the hydroxyethyl starch (HES) infusion could decrease OHSS incidence and severity. Prospective randomized study. The population under study consisted of women undergoing IVF cycles with GnRH agonist protocols, at risk of OHSS (more than 20 follicles observed larger than 12 mm in diameter and/or estradiol levels of 3000-5000 pg/mL). Women received a slow infusion of 500 mL of 6% HES during follicular aspiration alone or combined with 0.5mg cabergoline administration for 8 days, starting on the day of hCG administration. The rates of OHSS (both early and late) were very similar in the HES alone group (3.19% (3/94)) and in the HES plus cabergoline group (5.68% (5/88)), as were the rates of severe cases of OHSS (1.06% and 2.27%). Pregnancy rates (PR) were also similar in the two groups (ongoing PR per transfer, 47.56% and 47.50%). The co-administration of cabergoline in patients receiving HES due to OHSS risk did not reduce the rate or severity of OHSS in GnRH agonist IVF cycles. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep.

    Science.gov (United States)

    Hough, D; Bellingham, M; Haraldsen, I R; McLaughlin, M; Robinson, J E; Solbakk, A K; Evans, N P

    2017-03-01

    Chronic gonadotropin-releasing hormone agonist (GnRHa) administration is used where suppression of hypothalamic-pituitary-gonadal axis activity is beneficial, such as steroid-dependent cancers, early onset gender dysphoria, central precocious puberty and as a reversible contraceptive in veterinary medicine. GnRH receptors, however, are expressed outside the reproductive axis, e.g. brain areas such as the hippocampus which is crucial for learning and memory processes. Previous work, using an ovine model, has demonstrated that long-term spatial memory is reduced in adult rams (45 weeks of age), following peripubertal blockade of GnRH signaling (GnRHa: goserelin acetate), and this was independent of the associated loss of gonadal steroid signaling. The current study investigated whether this effect is reversed after discontinuation of GnRHa-treatment. The results demonstrate that peripubertal GnRHa-treatment suppressed reproductive function in rams, which was restored after cessation of GnRHa-treatment at 44 weeks of age, as indicated by similar testes size (relative to body weight) in both GnRHa-Recovery and Control rams at 81 weeks of age. Rams in which GnRHa-treatment was discontinued (GnRHa-Recovery) had comparable spatial maze traverse times to Controls, during spatial orientation and learning assessments at 85 and 99 weeks of age. Former GnRHa-treatment altered how quickly the rams progressed beyond a specific point in the spatial maze at 83 and 99 weeks of age, and the direction of this effect depended on gonadal steroid exposure, i.e. GnRHa-Recovery rams progressed quicker during breeding season and slower during non-breeding season, compared to Controls. The long-term spatial memory performance of GnRHa-Recovery rams remained reduced (P<0.05, 1.5-fold slower) after discontinuation of GnRHa, compared to Controls. This result suggests that the time at which puberty normally occurs may represent a critical period of hippocampal plasticity. Perturbing normal

  9. Pulmonary artery pulsatility and effect on vessel diameter assessment in magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Shariat, Masoud, E-mail: masoudshariat@gmail.com [Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Ontario (Canada); Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario (Canada); Schantz, Daryl, E-mail: daryl.schantz@gmail.com [Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario (Canada); Yoo, Shi-Joon, E-mail: shi-joon.yoo@sickkids.ca [Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario (Canada); Wintersperger, Bernd J., E-mail: bernd.wintersperger@uhn.ca [Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Ontario (Canada); Seed, Mike, E-mail: mike.seed@sickkids.ca [Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Cardiology, Hospital for Sick Children, Toronto, Ontario (Canada); Alnafisi, Bahiyah, E-mail: bahiyah.alnafisi@uhn.ca [Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Ontario (Canada); Chu, Leysia, E-mail: leysia_99@yahoo.com [Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario (Canada); MacGowan, Christopher K., E-mail: christopher.macgowan@sickkids.ca [Department of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Amerom, Joshua van, E-mail: Joshu.vanamerom@sickkids.ca [Department of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario (Canada); Grosse-Wortmann, Lars, E-mail: lars.grosse-wortmann@sickkids.ca [Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario (Canada); Department of Cardiology, Hospital for Sick Children, Toronto, Ontario (Canada)

    2014-02-15

    systolic cine SSFP or MRA in both groups (p < 0.0001). Vessel diameters measured on systolic SSFP were significantly larger than measurements made on diastolic SSFP (p < 0.0001). There was no significant difference between vessel measurements on MRA and measurements on systolic cine SSFP (p = 0.44 for the TOF group and p = 0.79 for ARVC group). Measurements on the MRA datasets were significantly larger than those on diastolic SSFP images (p < 0.0001). Conclusion: Black blood, white blood and MRA sequences are all reproducible CMR methods for the assessment of arterial diameters in children and adolescents. Measurements from systolic phase SSFP images are comparable to those from contrast-enhanced MRA. Therefore, the administration of contrast medium is not necessary in every case. Cine SSFP images offer the additional advantage over the other methods in such that both the largest and the smallest diameter of the vessel during the cardiac cycle can be assessed using this technique. This is even more relevant in highly pulsatile circulations, such as patients with repaired TOF and significant pulmonary insufficiency.

  10. A randomized trial of plasma volume expansion in hypertensive disorders of pregnancy: influence on the pulsatility indices of the fetal umbilical artery and middle cerebral artery

    NARCIS (Netherlands)

    Ganzevoort, W.; Rep, A.; Bonsel, G.J.; de Vries, J.I.P.; de Wolf, H.

    2005-01-01

    The purpose of this study was to investigate the effect of plasma volume expansion on the pulsatility indices of the fetal umbilical and middle cerebral arteries. Two hundred sixteen patients with severe preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome,

  11. Pulsatile Erlotinib in EGFR-Positive Non-Small-Cell Lung Cancer Patients With Leptomeningeal and Brain Metastases: Review of the Literature.

    Science.gov (United States)

    How, Joan; Mann, Janelle; Laczniak, Andrew N; Baggstrom, Maria Q

    2017-07-01

    Patients with epidermal growth factor receptor (EGFR)-positive (EGFR+) non-small-cell lung cancer (NSCLC) show improved response rates when treated with tyrosine kinase inhibitors (TKIs) such as erlotinib. However, standard daily dosing of erlotinib often does not reach therapeutic concentrations within the cerebrospinal fluid (CSF), resulting in progression of central nervous system (CNS) disease. Intermittent, high-dose administration of erlotinib reaches therapeutic concentrations within the CSF and is well tolerated in patients. Experience with "pulsatile" dosing, however, is limited. We review the literature on the pharmacology and clinical outcomes of pulsatile erlotinib in the treatment of EGFR+ NSCLC with brain and leptomeningeal metastases, and include available data on the use of next-generation TKIs in CNS progression. We also provide our institution's experience with patients treated with pulsatile erlotinib for CNS metastasis, and propose clinical criteria for its use. Pulsatile erlotinib is a reasonable alternative in EGFR+ patients with new or worsening CNS disease, without evidence of systemic progression, and without confirmed T790M resistance mutations within the CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. An investigation of pulsatile release tablets with ethylcellulose and Eudragit L as film coating materials and cross-linked polyvinylpyrrolidone in the core tablets.

    Science.gov (United States)

    Fan, T Y; Wei, S L; Yan, W W; Chen, D B; Li, J

    2001-12-13

    To develop new pulsatile release tablets, which can suppress drug release in stomach and release the drug rapidly after a predetermined lag time of about 3 h in intestine, the use of tablets with ethylcellulose/Eudragit L as a coating film and cross-linked polyvinylpyrrolidone in the core tablets was investigated. The release of diltiazem hydrochloride (DIL) as a model drug in the core tablets was investigated in vitro. The lag time (t10) was prolonged with an increase of the coating level, whereas the drug release rate was almost constant, irrespective of the coating level. The water-uptake study and electron microscope photographs suggested the mechanism of pulsatile release of drug. Pulsatile release tablets containing 60 mg DIL with 4.4 h of lag time (t10) in vitro were administrated to eight volunteers. The mean plasma concentration curves showed 4.9 h of lag time (tlag), 8.0 h of time to maximum concentration (tmax) and 3.1 h of time between tmax and tlag (t(psi)) in vivo. Relative bioavailability was 1.05 for pulsatile release tablets compared to conventional tablets.

  13. Roundtabling Sustainability

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2014-01-01

    The willingness of public authority to delegate social and environmental regulation to the private sector has varied from sector to sector, but has often led to the establishment of ‘voluntary’ standards and certifications on sustainability. Many of these have taken the form of ‘stewardship...... councils’ and ‘sustainability roundtables’ and have been designed around a set of institutional features seeking to establish legitimacy, fend off possible criticism, and ‘sell’ certifications to potential users. The concept of ‘roundtabling’ emphasizes the fitting a variety of commodity......-specific sustainability situations into a form that not only ‘hears more voices’ (as in ‘multi-stakeholder’), but also portrays to give them equal standing at the table of negotiations (roundtable), thus raising higher expectations on accountability, transparency and inclusiveness. In this article, I examine to what...

  14. Sustainability Evaluation.

    Science.gov (United States)

    Stichnothe, Heinz

    2017-03-17

    The long-term substitution of fossil resources can only be achieved through a bio-based economy, with biorefineries and bio-based products playing a major role. However, it is important to assess the implications of the transition to a bio-based economy. Life cycle-based sustainability assessment is probably the most suitable approach to quantify impacts and to identify trade-offs at multiple levels. The extended utilisation of biomass can cause land use change and affect food security of the most vulnerable people throughout the world. Although this is mainly a political issue and governments should be responsible, the responsibility is shifted to companies producing biofuels and other bio-based products. Organic wastes and lignocellulosic biomass are considered to be the preferred feedstock for the production of bio-based products. However, it is unlikely that a bio-based economy can rely only on organic wastes and lignocellulosic biomass.It is crucial to identify potential problems related to socio-economic and environmental issues. Currently there are many approaches to the sustainability of bio-based products, both quantitative and qualitative. However, results of different calculation methods are not necessarily comparable and can cause confusion among decision-makers, stakeholders and the public.Hence, a harmonised, globally agreed approach would be the best solution to secure sustainable biomass/biofuels/bio-based chemicals production and trade, and to avoid indirect effects (e.g. indirect land use change). However, there is still a long way to go.Generally, the selection of suitable indicators that serve the purpose of sustainability assessment is very context-specific. Therefore, it is recommended to use a flexible and modular approach that can be adapted to various purposes. A conceptual model for the selection of sustainability indicators is provided that facilitates identifying suitable sustainability indicators based on relevance and significance in a

  15. Effects of GnRH vaccination in wild and captive African Elephant bulls (Loxodonta africana on reproductive organs and semen quality.

    Directory of Open Access Journals (Sweden)

    Imke Lueders

    Full Text Available Although the African elephant (Loxodonta africana is classified as endangered by the International Union for Conservation of Nature (IUCN, in some isolated habitats in southern Africa, contraception is of major interest due to local overpopulation. GnRH vaccination has been promoted as a non-invasive contraceptive measure for population management of overabundant wildlife. We tested the efficacy of this treatment for fertility control in elephant bulls.In total, 17 male African elephants that were treated with a GnRH vaccine were examined in two groups. In the prospective study group 1 (n = 11 bulls, ages: 8-36 years, semen quality, the testes, seminal vesicles, ampullae and prostate, which were all measured by means of transrectal ultrasound, and faecal androgen metabolite concentrations were monitored over a three-year period. Each bull in the prospective study received 5 ml of Improvac® (1000 μg GnRH conjugate intramuscularly after the first examination, followed by a booster six weeks later and thereafter every 5-7 months. In a retrospective study group (group 2, n = 6, ages: 19-33 years, one examination was performed on bulls which had been treated with GnRH vaccine for 5-11 years.In all bulls of group 1, testicular and accessory sex gland sizes decreased significantly after the third vaccination. In six males examined prior to vaccination and again after more than five vaccinations, the testis size was reduced by 57.5%. Mean testicular height and length decreased from 13.3 ± 2.6 cm x 15.2 ± 2.8 cm at the beginning to 7.6 ± 2.1 cm x 10.2 ± 1.8 cm at the end of the study. Post pubertal bulls (>9 years, n = 6 examined prior to vaccination produced ejaculates with viable spermatozoa (volume: 8-175 ml, sperm concentration: 410-4000x106/ml, total motility: 0-90%, while after 5-8 injections, only 50% of these bulls produced ejaculates with a small number of immotile spermatozoa. The ejaculates of group 2 bulls (vaccinated >8 times were

  16. Antibodies against gonadotropin-releasing hormone (GnRH) in patients with diabetes mellitus is associated with lower body weight and autonomic neuropathy.

    Science.gov (United States)

    Berntorp, Kerstin; Frid, Anders; Alm, Ragnar; Fredrikson, Gunilla Nordin; Sjöberg, Klas; Ohlsson, Bodil

    2013-08-17

    Esophageal dysmotility and gastroparesis are common secondary complications in patients with diabetes mellitus. Patients with dysmotility express antibodies against gonadotropin-releasing hormone (GnRH) in serum. The aim of the present study was to scrutinize patients with diabetes mellitus with regard to the presence of GnRH antibodies, and to examine associations between antibodies and clinical findings. Thirty-nine consecutive patients with diabetes mellitus were included in the study after clinical examination and examination by esophageal manometry and gastric emptying scintigraphy. Serum was analyzed for the presence of antibodies against GnRH using an ELISA, and values are expressed as relative units (RU). Two age- and gender-matched healthy subjects per each patient served as controls. The prevalence of IgM GnRH antibodies in patients was 33% compared to 14% in controls (p = 0.027), with a higher antibody titer; 1.2 (0.6-5.0) and 0.2 (0.1-0.3) RU, respectively (p = 0.000). The expression of IgG antibodies was 15% in patients and none in controls (p = 0.000). Lower body mass index was associated with the presence of IgM antibodies (OR = 0.835, 95% CI = 0.699-0.998), and autonomic neuropathy with the presence IgG antibodies (OR = 9.000, 95% CI = 1.327-61.025). Esophageal dysmotility (69%) or gastroparesis (18%) were not associated with the presence of IgM antibodies (OR = 0.589, 95% CI = 0.143-2.424 and OR = 3.407, 95% CI = 0.633-18.350, respectively). Neither was esophageal dysmotility associated with IgG antibodies (OR = 2.500, 95% CI = 0.259-24.096). Antibodies against GnRH are more common in patients with diabetes mellitus compared with healthy controls. IgM antibodies are associated with lower body mass index and IgG antibodies are associated with autonomic neuropathy.

  17. Photoperiod-independent changes in immunoreactive brain gonadotropin-releasing hormone (GnRH) in a free-living, tropical bird.

    Science.gov (United States)

    Moore, Ignacio T; Bentley, George E; Wotus, Cheryl; Wingfield, John C

    2006-01-01

    Timing of seasonal reproduction in high latitude vertebrates is generally regulated by photoperiodic cues. Increasing day length in the spring is associated with changes in the brain that are responsible for mediating reproductive activities. A primary example of this is the increased content of gonadotropin-releasing hormone (GnRH) in the preoptic area of the hypothalamus in birds as they enter the spring breeding season. Increased GnRH activity stimulates the release of luteinizing hormone and follicle-stimulating hormone from the anterior pituitary. These gonadotropins induce growth of the gonads and release of sex steroids which act on the brain to mediate reproductive behaviors. By contrast, seasonal breeding in the tropics can occur in the absence of significant changes in photoperiod. To our knowledge, no studies have investigated whether seasonal breeding in free-living tropical vertebrates is associated with seasonal changes in the GnRH system. We studied two populations of rufous-collared sparrows (Zonotrichia capensis) at the equator, separated by only 25 km, but with asynchronous reproductive phenologies associated with local climate and independent of photoperiodic cues. We collected brains and measured GnRH immunoreactivity (GnRH-ir) during each population's breeding and non-breeding periods. Breeding males had larger, but not more, GnRH-ir cells than non-breeding birds. The plasticity of the GnRH system was associated with local climate, such that the two populations exhibited asynchronous changes in GnRH-ir despite experiencing identical photoperiod conditions. Our results demonstrate that tropical birds can exhibit neural changes similar to those exhibited in higher latitude birds. However, these tropical populations appear to be using supplementary cues (e.g., rainfall, temperature, food availability) in a similar way to higher latitude species using an initial predictive cue (photoperiod). These results raise questions about the evolution of

  18. Evidence for Changes in Numbers of Synaptic Inputs onto KNDy and GnRH Neurones during the Preovulatory LH Surge in the Ewe.

    Science.gov (United States)

    Merkley, C M; Coolen, L M; Goodman, R L; Lehman, M N

    2015-07-01

    Kisspeptin neurones located in the arcuate nucleus (ARC) and preoptic area (POA) are critical mediators of gonadal steroid feedback onto gonadotrophin-releasing hormone (GnRH) neurones. ARC kisspeptin cells that co-localise neurokinin B (NKB) and dynorphin (Dyn), are collectively referred to as KNDy (Kisspeptin/NKB/Dyn) neurones, and have been shown in mice to also co-express the vesicular glutamate transporter, vGlut2, an established glutamatergic marker. The ARC in rodents has long been known as a site of hormone-induced neuroplasticity, and changes in synaptic inputs to ARC neurones in rodents occur over the oestrous cycle. Based on this evidence, the the present study aimed to examine possible changes across the ovine oestrous cycle in synaptic inputs onto kisspeptin cells in the ARC (KNDy) and POA, and inputs onto GnRH neurones. Gonadal-intact breeding season ewes were perfused using 4% paraformaldehyde during either the luteal or follicular phase of the oestrous cycle, with the latter group killed at the time of the luteinising hormone (LH) surge. Hypothalamic sections were processed for triple-label immunodetection of kisspeptin/vGlut2/synaptophysin or kisspeptin/vGlut2/GnRH. The total numbers of synaptophysin- and vGlut2-positive inputs to ARC KNDy neurones were significantly increased at the time of the LH surge compared to the luteal phase; because these did not contain kisspeptin, they do not arise from KNDy neurones. By contrast to the ARC, the total number of synaptophysin-positive inputs onto POA kisspeptin neurones did not differ between luteal phase and surge animals. The total number of kisspeptin and vGlut2 inputs onto GnRH neurones in the mediobasal hypothalamus (MBH) was also increased during the LH surge, and could be attributed to an increase in the number of KNDy (double-labelled kisspeptin + vGlut2) inputs. Taken together, these results provide novel evidence of synaptic plasticity at the level of inputs onto KNDy and GnRH neurones during

  19. Evidence for changes in numbers of synaptic inpcuts onto KNDy and GnRH neurones during the preovulatory LH surge in the ewe

    Science.gov (United States)

    Merkley, Christina M.; Coolen, Lique M.; Goodman, Robert L.; Lehman, Michael N.

    2016-01-01

    Kisspeptin neurones located in the arcuate nucleus (ARC) and preoptic area (POA) are critical mediators of gonadal steroid feedback onto GnRH neurones. ARC kisspeptin cells that co-localize neurokinin B (NKB) and dynorphin (Dyn), are collectively referred to as KNDy (Kisspeptin/NKB/Dyn) neurones, and have been shown to also co-express the glutamatergic marker, vGlut2, in mice. The ARC in rodents has long been known as a site of hormone-induced neuroplasticity, and changes in synaptic inputs to ARC neurones in rodents occur over the oestrous cycle. Based on this evidence, the goal of this study was to examine possible changes across the ovine oestrous cycle in synaptic inputs onto kisspeptin cells in the ARC (KNDy) and POA, and inputs onto GnRH neurones. Gonadal-intact breeding season ewes were perfused using 4% paraformaldehyde during either the luteal or follicular phase of the oestrous cycle, the latter group sacrificed at the time of the luteinising (LH) surge. Hypothalamic sections were processed for triple-label immunodetection of kisspeptin/vGlut2/synaptophysin or kisspeptin/vGlut2/GnRH. The total numbers of synaptophysin- and vGlut2-positive inputs to ARC KNDy neurones were significantly increased at the time of the LH surge compared to luteal phase; as these did not contain kisspeptin they do not arise from KNDy neurons. In contrast to the ARC, the total number of synaptophysin-positive inputs onto POA kisspeptin neurones did not differ between luteal phase and surge animals. The total number of kisspeptin and vGlut2 inputs onto GnRH neurones in both the POA and mediobasal hypothalamus was also increased during the LH surge. Taken together, these results provide novel evidence of synaptic plasticity at the level of inputs onto KNDy and GnRH neurones during the ovine oestrous cycle, changes which may contribute to the generation of the preovulatory GnRH/LH surge. PMID:25976424

  20. In search of the molecular mechanisms mediating the inhibitory effect of the GnRH antagonist degarelix on human prostate cell growth.

    Directory of Open Access Journals (Sweden)

    Monica Sakai

    Full Text Available Degarelix is a gonadrotropin-releasing hormone (GnRH receptor (GnRHR antagonist used in patients with prostate cancer who need androgen deprivation therapy. GnRHRs have been found in extra-pituitary tissues, including prostate, which may be affected by the GnRH and GnRH analogues used in therapy. The direct effect of degarelix on human prostate cell growth was evaluated. Normal prostate myofibroblast WPMY-1 and epithelial WPE1-NA22 cells, benign prostatic hyperplasia (BPH-1 cells, androgen-independent PC-3 and androgen-dependent LNCaP prostate cancer cells, as well as VCaP cells derived from a patient with castration-resistant prostate cancer were used. Discriminatory protein and lipid fingerprints of normal, hyperplastic, and cancer cells were generated by matrix-assisted laser desorption/ionization (MALDI mass spectrometry (MS. The investigated cell lines express GNRHR1 and GNRHR2 and their endogenous ligands. Degarelix treatment reduced cell viability in all prostate cell lines tested, with the exception of the PC-3 cells; this can be attributed to increased apoptosis, as indicated by increased caspase 3/7, 8 and 9 levels. WPE1-NA22, BPH-1, LNCaP, and VCaP cell viability was not affected by treatment with the GnRH agonists leuprolide and goserelin. Using MALDI MS, we detected changes in m/z signals that were robust enough to create a complete discriminatory profile induced by degarelix. Transcriptomic analysis of BPH-1 cells provided a global map of genes affected by degarelix and indicated that the biological processes affected were related to cell growth, G-coupled receptors, the mitogen-activated protein kinase (MAPK pathway, angiogenesis and cell adhesion. Taken together, these data demonstrate that (i the GnRH antagonist degarelix exerts a direct effect on prostate cell growth through apoptosis; (ii MALDI MS analysis provided a basis to fingerprint degarelix-treated prostate cells; and (iii the clusters of genes affected by degarelix

  1. Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Oliveira João

    2010-09-01

    Full Text Available Abstract Background The effects of gonadotrophin-releasing hormone agonist (GnRH-a administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes. Methods The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures. Results All cycles presented statistically significantly higher rates of implantation (P Conclusions These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

  2. Hormonal characteristics of follicular fluid from women receiving either GnRH agonist or hCG for ovulation induction

    DEFF Research Database (Denmark)

    Andersen, C Yding; Al Humaidan, Peter Samir Heskjær; Ejdrup, H Bredkjaer

    2006-01-01

    BACKGROUND: A recent prospective randomized study from our group compared GnRH agonist (0.5 mg buserelin) and hCG (10,000 IU) for triggering of ovulation following a flexible antagonist protocol. The agonist group showed a poor reproductive outcome despite luteal phase support with progesterone......-ovulatory follicular maturation resulting in oocytes with a compromised developmental competence. METHODS: Hormone concentrations were measured in two individual follicular fluid samples from each of 32 women receiving buserelin and 37 receiving hCG, thus representing a subset of the follicles retrieved. RESULTS......: Follicular fluid levels of LH in the agonist group as compared with the hCG group was 11.1 +/- 0.5 versus 3.6 +/- 0.3 IU/l (mean +/- SEM; P hCG, not determined versus 139+/-8 IU/l; E(2), 1.9 +/- 0.2 versus 1.8 +/- 0.2 micromol/l (P > 0...

  3. Evaluation of Pre and Post Artificial Insemination effect of GnRH Hormone on conception of repeat breeder Deoni Cows

    Directory of Open Access Journals (Sweden)

    S.D. Awati

    2010-10-01

    Full Text Available Twenty four Deoni repeat breeder cows were randomly allocated into 4 groups of six each. The animals of groups I, II and III were injected with 250 µg of buserelin acetate (Receptal® on two occasions i.e. once on day of estrus and second dose on days 10 or 12 or14 respectively in I, II and III groups following breeding, while the animals of group IV served as control. Among the physical characters of estrual cervico-vaginal mucous, typical arborization pattern (80.95 % in pregnant vs. 55.56 % in non-pregnant cows and marginally high spinnbarkeit readings (24.67+2.7cms in pregnant and 22.21+1.32 cms in non-pregnant cows favored better fertility, although the differences between the groups were statistically insignificant. However, the pH of estrual cervico-vaginal mucous did not indicate any effect on fertility and it ranged between 8.00 to 9.00. The cows of treatment groups I, II and III registered a considerably higher conception rate of 83.33 percent each, while in control group cows had only 33.33 percent. To conclude GnRH therapy irrespective of days of administration resulted in an overall enhancement in conception rate of 83.33 as against 33.33 percent in control groups of cows. [Vet. World 2010; 3(5.000: 209-211

  4. Effect of the Pulsatile Extracorporeal Membrane Oxygenation on Hemodynamic Energy and Systemic Microcirculation in a Piglet Model of Acute Cardiac Failure.

    Science.gov (United States)

    Itoh, Hideshi; Ichiba, Shingo; Ujike, Yoshihito; Douguchi, Takuma; Obata, Hideaki; Inamori, Syuji; Iwasaki, Tatsuo; Kasahara, Shingo; Sano, Shunji; Ündar, Akif

    2016-01-01

    The objective of this study was to compare the effects of pulsatile and nonpulsatile extracorporeal membrane oxygenation (ECMO) on hemodynamic energy and systemic microcirculation in an acute cardiac failure model in piglets. Fourteen piglets with a mean body weight of 6.08 ± 0.86 kg were divided into pulsatile (N = 7) and nonpulsatile (N = 7) ECMO groups. The experimental ECMO circuit consisted of a centrifugal pump, a membrane oxygenator, and a pneumatic pulsatile flow generator system developed in-house. Nonpulsatile ECMO was initiated at a flow rate of 140 mL/kg/min for the first 30 min with normal heart beating, with rectal temperature maintained at 36°C. Ventricular fibrillation was then induced with a 3.5-V alternating current to generate a cardiac dysfunction model. Using this model, we collected the data on pulsatile and nonpulsatile groups. The piglets were weaned off ECMO at the end of the experiment (180 min after ECMO was initiated). The animals did not receive blood transfusions, inotropic drugs, or vasoactive drugs. Blood samples were collected to measure hemoglobin, methemoglobin, blood gases, electrolytes, and lactic acid levels. Hemodynamic energy was calculated using the Shepard's energy equivalent pressure. Near-infrared spectroscopy was used to monitor brain and kidney perfusion. The pulsatile ECMO group had a higher atrial pressure (systolic and mean), and significantly higher regional saturation at the brain level, than the nonpulsatile group (for both, P energy and improves systemic microcirculation, compared with nonpulsatile ECMO in acute cardiac failure. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  5. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type.

    Science.gov (United States)

    Lambalk, C B; Banga, F R; Huirne, J A; Toftager, M; Pinborg, A; Homburg, R; van der Veen, F; van Wely, M

    2017-09-01

    Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist was not the only variable between the compared study arms. The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. The Cochrane Menstrual Disorders and Subfertility Review Group specialized register of controlled trials and Pubmed and Embase databases were searched from inception until June 2016. Eligible trials were those that compared GnRH antagonist protocols and standard long GnRH agonist protocols in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF population, women with PCOS and women with poor ovarian response. Pre-planned subgroup analyses were performed for various antagonist treatment schedules. We included 50 studies. Of these, 34 studies reported on general IVF patients, 10 studies reported on PCOS patients and 6 studies reported on poor responders. In general IVF patients, ongoing pregnancy rate was significantly lower in the antagonist group compared with the agonist group (RR 0.89, 95% CI 0.82-0.96). In women with PCOS and in women with poor ovarian response, there was no evidence of a difference in ongoing pregnancy between the antagonist and agonist groups (RR 0.97, 95% CI 0.84-1.11 and RR 0.87, 95% CI 0.65-1.17, respectively). Subgroup analyses for various antagonist treatment schedules compared to the long protocol GnRH agonist showed a significantly lower ongoing

  6. Impact of phase of the estrous cycle and season on LH surge profile and fertility in dairy cows treated with different GnRH analogs (gonadorelin vs. buserelin).

    Science.gov (United States)

    Armengol-Gelonch, R; Mallo, J M; Ponté, D; Jimenez, A; Valenza, A; Souza, A H

    2017-03-15

    Our aim was to assess the GnRH-induced LH surge profile in dairy cows receiving two GnRH products (gonadorelin vs buserelin) given at proestrus or diestrus phase and to investigate whether season could alter LH surge profile in dairy cows. In Experiment 1, dairy cows at 108.2 ± 2.3 DIM, producing 41.5 ± 0.3 kg/day were randomized to receive, during proestrus and diestrus: Ovarelin® i.m. (OVA; n = 56; 100 mg of gonadorelin diacetate tetrahydrate; Ceva Animal Health, France) or Receptal® i.m. (REC; n = 52; 10 mcg of buserelin diacetate; MSD, Germany). In Experiment 1, blood samples were collected at hour 0 (just before GnRH treatment) at 30min, 1 h and then hourly until 5 h post-GnRH. In Experiment 2, cows were synchronized with a modified G-6-G protocol and randomized to receive either OVA or REC throughout the synchronization program. In Experiment 1, peak LH concentrations (ng/mL) were not affected by type of GnRH (OVA = 6.2 ± 0.4 vs REC = 6.7 ± 0.4; P = 0.37) or season (Cool = 6.8 ± 0.4 vs Warm = 6.1 ± 0.4; P = 0.22), and there were no interactions between GnRH type and phase of the estrous cycle or season. Interestingly, the area under the curve (AUC) of LH release (ng/ml*time) was significantly lower during warmer months (Cool = 20.3 ± 1.2 vs Warm = 16.9 ± 1.1; P = 0.04). As expected, LH peak was affected by phase of the cycle (proestrus = 8.2 ± 0.4 vs diestrus = 4.7 ± 0.4; P surge profile and cows during warm season had reduced AUC. Additionally, type of GnRH did not influence LH surge profile and P/AI in synchronized cows. Regardless of GnRH type, strategies to avoid heat stress and excessively high levels of circulating P4 near the time of GnRH treatment might help improve LH release profile in dairy cows, and ultimately increase P/AI. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effect of Administration of Single Dose GnRH Agonist in Luteal Phase on Outcome of ICSI-ET Cycles in Women with Previous History of IVF/ICSI Failure: A Randomized Controlled Trial

    Science.gov (United States)

    Zafardoust, Simin; Jeddi-Tehrani, Mahmood; Akhondi, Mohammad Mehdi; Sadeghi, Mohammad Reza; Kamali, Koroush; Mokhtar, Sara; Badehnoosh, Bita; Arjmand-Teymouri, Fatemeh; Fatemi, Farnaz; Mohammadzadeh, Afsaneh

    2015-01-01

    Background GnRH agonist administration in the luteal phase has been suggested to beneficially affect the outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This blind randomized controlled study evaluates the effect of GnRH (Gonadotropine Releasing Hormone) agonist administration on ICSI outcome in GnRH antagonist ovarian stimulation protocol in women with 2 or more previous IVF/ICSI-ET failures. Methods One hundred IVF failure women who underwent ICSI cycles and stimulated with GnRH antagonist ovarian stimulation protocol, were included in the study. Women were randomly assigned to intervention (received a single dose injection of GnRH agonist (0.1 mg of Decapeptil) subcutaneously 6 days after oocyte retrieval) and control (did not receive GnRH agonist) groups. Implantation and clinical pregnancy rates were the primary outcome measures. Results Although the age of women, the number of embryos transferred in the current cycle and the quality of the transferred embryos were similar in the two groups, there was a significantly higher rate of implantation (Mann Whitney test, p = 0.041) and pregnancy (32.6% vs. 12.5%, p = 0.030, OR = 3.3, 95%CI, 1.08 to 10.4) in the intervention group. Conclusion Our results suggested that, in addition to routine luteal phase support using progesterone, administration of 0.1 mg of Decapeptil 6 days after oocyte retrieval in women with previous history of 2 or more IVF/ICSI failures led to a significant improvement in implantation and pregnancy rates after ICSI following ovarian stimulation with GnRH antagonist protocol. PMID:25927026

  8. The forebrain-midbrain acts as functional endocrine signaling pathway of Kiss2/Gnrh1 system controlling the gonadotroph activity in the teleost fish European sea bass (Dicentrarchus labrax).

    Science.gov (United States)

    Espigares, Felipe; Carrillo, Manuel; Gómez, Ana; Zanuy, Silvia

    2015-03-01

    Some teleost species, including European sea bass, harbor two different kisspeptin coding genes: kiss1 and kiss2. Both genes are expressed in the brain, but their differential roles in the central control of fish reproduction are only beginning to be elucidated. In this study, we have examined the effects of intracerebroventricular injections of the highly active sea bass peptides Kiss1-15 and Kiss2-12 on spermiating male sea bass. Physiological saline, Kiss1-15, or Kiss2-12 was injected into the third ventricle. To establish the gene expression cascade involved in the action of kisspeptins, the expression of the two sea bass kisspeptin receptor genes (kiss1r and kiss2r) and the three sea bass Gnrh genes (gnrh1, gnrh2, and gnrh3) were analyzed in the forebrain-midbrain and the hypothalamus. In addition, the protein levels of hypothalamic and pituitary Gnrh1 were measured. Blood samples were collected at different times after injection to analyze the effects of kisspeptins on the release of gonadotropins (Lh and Fsh) and androgens (testosterone and 11-ketotestosterone). The present results provide the first evidence that the effects of Kiss2 on central regulation of reproductive function involve the neuroendocrine areas of the forebrain-midbrain in teleost fish. The marked effect of Kiss2 on kiss2r and gnrh1 expression in the forebrain-midbrain and on Gnrh1 release suggest that this neuronal system is involved in the neuroendocrine regulation of gonadotroph activity. This hypothesis was confirmed by a surge of plasma Lh in response to Kiss2, which presumably has a strong stimulatory effect on testosterone release, and thus on sperm quality parameters. © 2015 by the Society for the Study of Reproduction, Inc.

  9. Sustainable Soesterkwartier

    NARCIS (Netherlands)

    Abrahams, H.; Goosen, H.; Jong, de F.; Sickmann, J.; Prins, D.

    2010-01-01

    The municipality of Amersfoort wants to construct an endurable and sustainable eco-town in the Soesterkwartier neighbourhood, by taking future climate change into account. The impact of climate change at the location of the proposed eco-town was studied by a literature review.

  10. Sustainable agriculture

    International Development Research Centre (IDRC) Digital Library (Canada)

    New farming techniques, better food security. Since 1970, IDRC-supported research has introduced sustainable agricultural practices to farmers and communities across the devel- oping world. The result: higher productivity, less poverty, greater food security, and a healthier environment. Opportunities grow on trees in ...

  11. Sustainable Development

    African Journals Online (AJOL)

    Tsegai Berhane Ghebretekle

    Abstract. This article examines the concept of sustainable development after the Post-. 2015 Paris Climate Change Agreement with particular emphasis on Ethiopia. Various African countries are vulnerable to climate change, as is evidenced by recent droughts. Ethiopia is selected as a case study in light of its pace in.

  12. Sustainable machining

    CERN Document Server

    2017-01-01

    This book provides an overview on current sustainable machining. Its chapters cover the concept in economic, social and environmental dimensions. It provides the reader with proper ways to handle several pollutants produced during the machining process. The book is useful on both undergraduate and postgraduate levels and it is of interest to all those working with manufacturing and machining technology.

  13. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The

  14. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. It The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  15. Exergy sustainability.

    Energy Technology Data Exchange (ETDEWEB)

    Robinett, Rush D. III (.; ); Wilson, David Gerald; Reed, Alfred W.

    2006-05-01

    Exergy is the elixir of life. Exergy is that portion of energy available to do work. Elixir is defined as a substance held capable of prolonging life indefinitely, which implies sustainability of life. In terms of mathematics and engineering, exergy sustainability is defined as the continuous compensation of irreversible entropy production in an open system with an impedance and capacity-matched persistent exergy source. Irreversible and nonequilibrium thermodynamic concepts are combined with self-organizing systems theories as well as nonlinear control and stability analyses to explain this definition. In particular, this paper provides a missing link in the analysis of self-organizing systems: a tie between irreversible thermodynamics and Hamiltonian systems. As a result of this work, the concept of ''on the edge of chaos'' is formulated as a set of necessary and sufficient conditions for stability and performance of sustainable systems. This interplay between exergy rate and irreversible entropy production rate can be described as Yin and Yang control: the dialectic synthesis of opposing power flows. In addition, exergy is shown to be a fundamental driver and necessary input for sustainable systems, since exergy input in the form of power is a single point of failure for self-organizing, adaptable systems.

  16. Sustainable processing

    DEFF Research Database (Denmark)

    Kristensen, Niels Heine

    2004-01-01

    Kristensen_NH and_Beck A: Sustainable processing. In Otto Schmid, Alexander Beck and Ursula Kretzschmar (Editors) (2004): Underlying Principles in Organic and "Low-Input Food" Processing - Literature Survey. Research Institute of Organic Agriculture FiBL, CH-5070 Frick, Switzerland. ISBN 3-906081-58-3...

  17. Sustainable finance

    NARCIS (Netherlands)

    dr. Margreet F. Boersma-de Jong

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence

  18. Simulator training on pulsatile vascular models significantly improves surgical skills and the quality of carotid patch plasty.

    Science.gov (United States)

    Duschek, Nikolaus; Assadian, Afshin; Lamont, Peter M; Klemm, Klaus; Schmidli, Jürg; Mendel, Herbert; Eckstein, Hans-Henning

    2013-04-01

    Vascular surgeons perform numerous highly sophisticated and delicate procedures. Due to restrictions in training time and the advent of endovascular techniques, new concepts including alternative environments for training and assessment of surgical skills are required. Over the past decade, training on simulators and synthetic models has become more sophisticated and lifelike. This study was designed to evaluate the impact of a 3-day intense training course in open vascular surgery on both specific and global vascular surgical skills. Prospective observational cohort analysis with various parameter measurements of both surgical skills and the technical quality of the finished product, performed before and after 3 days of simulator training of 10 participants (seven male and three female) in a vascular surgery training course. The simulator model used was a conventional carotid endarterectomy with a Dacron patch plasty on a lifelike carotid bench model under pulsatile pressure. The primary end points were assessment of any changes in the participants' surgical skills and in the technical quality of their completed carotid patches documented by procedure-based assessment forms. Scores ranging from 1 (inadequate) to 5 (excellent) were compared by a related-sample Wilcoxon signed test. Interobserver reliability was estimated by Cronbach's alpha (CA). A significant improvement in surgical skills tasks was observed (P quality of the carotid patch increased significantly by 0.96 (27%) from fair (3.55 ± 0.87) to satisfactory (4.51 ± 0.76; P quality of the carotid patch was acceptable (CA = 0.713) and for surgical skills was low (CA = 0.424). This study shows that lifelike simulation featuring pulsatile flow can increase surgical skills and technical quality in a highly sophisticated multistep vascular intervention. This training provides comparatively inexpensive and lifelike training possibilities for the adoption and assessment of surgical skills required to perform

  19. An in vitro study of pulsatile fluid dynamics in intracranial aneurysm models treated with embolic coils and flow diverters.

    Science.gov (United States)

    Babiker, M Haithem; Gonzalez, L Fernando; Albuquerque, Felipe; Collins, Daniel; Elvikis, Arius; Zwart, Christine; Roszelle, Breigh; Frakes, David H

    2013-04-01

    Although coil embolization is one of the most effective treatments for intracranial aneurysms (ICAs), the procedure is often unsuccessful. For example, an ICA may persist after coil embolization if deployed coils fail to block the flow of blood into the aneurysm. Unfortunately, the specific flow changes that are effected by embolic coiling (and other endovascular therapies) are poorly understood, which creates a barrier to the design and execution of optimal treatments in the clinic. We present an in vitro pulsatile flow study of treated basilar tip aneurysm models that elucidates relationships between controllable treatment parameters and clinically important post-treatment fluid dynamics. We also compare fluid dynamic performance across embolic coils and more recently proposed devices (e.g., the Pipeline Embolization Device) that focus on treating ICAs by diverting rather than blocking blood flow. In agreement with previous steady flow studies, coil embolization-reduced velocity magnitude at the aneurysmal neck by greater percentages for a narrow-neck aneurysm, and reduced flow into aneurysms by greater percentages at lower parent vessel flow rates. However, flow diversion reduced flow into a wide-neck aneurysm more so than coil embolization, regardless of flow conditions. Finally, results also showed that for the endovascular devices we examined, treatment effects were generally less dramatic under physiologic pulsatile flow conditions as compared to steady flow conditions. The fluid dynamic performance data presented in this study represent the first direct in vitro comparison of coils and flow diverters in aneurysm models, and provide a novel, quantitative basis to aid in designing endovascular treatments toward specific fluid dynamic outcomes.

  20. Experimental and theoretical investigations of Lantana camara oil diffusion from polyacrylonitrile membrane for pulsatile drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Vivek [Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune 411008 (India); Balasubramanian, K., E-mail: meetkbs@gmail.com [Department of Materials Engineering, Defence Institute of Advance Technology (DIAT), Ministry of Defence, Girinagar, Pune 411025 (India)

    2014-08-01

    Porous composite membrane of polyacrylonitrile (PAN) and Lantana camara essential oil was synthesized by solvent casting method. Stability of oil in PAN solution was measured by XiGo nano tool indicating constant relaxation time of 1487 time/s. Pore size of few microns confirmed by electron microscopy was supported by atomic force microscopy indicating roughness factor of 0.9 nm. Contact angle of 2° inveterates superhydrophilicity of the composite membrane. Membrane showed excellent antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli with a 7–10 mm zone of inhibition. In vitro release of Lantana oil from the composite membrane was carried out in isotonic phosphate buffer solution (pH = 7.4). Lantana oil was released for 9 h, lag time of 3 h with constant 33% release confirmed PAN membranes as potential system for pulsatile drug delivery applications. Diffusion of E-caryophyllene (antibacterial component of oil) which was studied through molecular simulation using Material Studio software ensued diffusion coefficient value of 1.11 ∗ 10{sup −9} m{sup 2}/s. Biocompatibility of the composite membrane was assessed by mouse embryonic fibroblast cell line (NIH 3T3) through MTT assay indicating more than 91% viable cell even at 200 μg/mL concentration. Such membranes can be efficiently used in biomedical applications as antibacterial and antifungal agent. - Highlights: • Pulsatile release • Lantana oil–PAN composite membrane as antibacterial material • Enhanced bactericidal activity of the membrane.

  1. SUSTAINABLE CORPORATE AND SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    DORU CÎRNU

    2017-06-01

    Full Text Available In recent decades, the image of the international business environment has changed significantly. Studies conducted by UNCTAD shows that corporate phenomenon developments in the world economy is growing. Without claiming to present an exhaustive topic so vast we tried to capture some "facets" of sustainable development from the perspective of multinational corporations, given the expansion of these economic entities and strengthening their power in the global economy. We present more negative aspects of the actions of multinational corporations in terms of sustainable development, it is very important to know both sides of the coin, which will not only help transnational giants including release. Based on issues such as corporate social responsibility, environmental pollution and workers' rights, we sought to counter official statements. The conclusion is that these economic entities are real forces that can not be ignored in today's world and the obvious problem of sustainable development can not be addressed independently of the phenomenon, context we also identified some possible solutions to conflict of corporations and essence of the concept of sustainable development.

  2. Radioimmunoassay for GnRH agonist analogue in serum of patients with prostate cancer treated with D-Ser (tBu)/sup 6/AZA gly/sup 10/ GnRH

    Energy Technology Data Exchange (ETDEWEB)

    Clayton, R.N.; Bailey, L.C.; Cottam, J.; Arkell, D.; Perren, T.J.; Blackledge, G.R.P. (Birmingham Univ. (UK). Dept. of Medicine; Dudley Road Hospital, Birmingham (UK))

    1985-04-01

    A radioimmunoassay is described for D-Ser (tBu)/sup 6/ AZA Gly/sup 10/ GnRH (ICI 118630) in serum of prostate cancer patients treated chronically with this peptide to produce castration. With /sup 125/I-118630 as the label, and an anti-GnRH serum, the specificity of the assay is directed to the N-terminal end of the peptide, and putative degradation products have <6% cross-reactivity. The assay appears specific for intact 118630 which, after subcutaneous administration of 250 ..mu..g, has a half-time of disappearance from the serum of 4.9 +- 0.4 h and a volume of distribution of 13.7 +- 0.8 litres. Continuous subcutaneous infusion of 120 ..mu..g 118630/d gave stable serum concentrations of between 2-3 ng/ml for up to 63 d which were very similar to values predicted from pharmacokinetic analysis of the analogue clearance rate. This contrasts with the 'peak and trough' pattern of serum 118630 levels measured in two subjects after 118630 administration from a subcutaneous implant containing 3.6 mg of peptide in a biodegradable formulation. Serum 118630 levels peaked between 6-8 ng/ml 15 d after the implant, falling to <1 ng/ml at 29 d, immediately before the next implant. Serum 118630 levels following a second 3.6 mg implant were almost identical with respect to absolute concentration and time to peak value.

  3. Sustainable Consumption

    DEFF Research Database (Denmark)

    Røpke, Inge

    2015-01-01

    in wider social, economic and technological frameworks is emphasised. In particular, the chapter is inspired by practice theory and transition theory. First, various trends in consumption are outlined to highlight some of the challenges for sustainability transitions. Then, it is discussed how consumption...... patterns are shaped over time and what should be considered in sustainability strategies. While discussions on consumption often take their point of departure in the perspective of the individual and then zoom to the wider context, the present approach is the opposite. The outline starts with the basic...... biophysical, distributional and economic conditions for high consumption in rich countries and then zooms in on the coevolution of provision systems and consumption, and how consumption is shaped by practices and projects in everyday life. Furthermore, the paper discusses whether and how transition...

  4. Sustainable Buildings

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Elle, Morten

    The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems that ...... that need urgent action. The built environment is an obvious area to put effort into because of the large and cost-effective energy saving potential and potential for Renewable Energy-based supply systems for buildings.......The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems...

  5. The effect of GnRH or oestradiol injected at pro-oestrus on luteal function and follicular dynamics of the subsequent oestrous cycle in non-lactating cycling Holstein cows

    Directory of Open Access Journals (Sweden)

    B.V.E. Segwagwe

    2006-09-01

    Full Text Available Oestrous synchronization involves synchronization of ovarian follicular turnover, new wave emergence, and finally induction of ovulation. The final step can be synchronized by the parenteral administration of either GnRH or oestradiol benzoate. This study investigated corpus luteum and follicular emergence after ovulation had been induced by the administration of either GnRH or oestradiol benzoate. The injection of oestradiol benzoate may have delayed the emergence of the first follicular wave subsequent to the induced ovulation; administration of oestradiol benzoate or GnRH lowered the progesterone rise so that the maximum dioestrous concentration of progesterone on Day 9 was lower when cows were treated during pro-oestrus compared to the spontaneously ovulating controls. One implication of findings from the present study is that induction of ovulation with either oestradiol benzoate or GnRH, administered 24 or 36 h after withdrawal of the CIDR device, respectively, may lower fertility. Future studies must identify the timing of administration relative to the time of CIDR device withdrawal and the optimum concentration of oestradiol benzoate or GnRH that would not have untoward effects on the development of the corpus lutea, particularly within the first week of dioestrus.

  6. The Potential Role of GnRH Agonists and Antagonists in Inducing Thyroid Physiopathological Changes During IVF.

    Science.gov (United States)

    Gizzo, Salvatore; Noventa, Marco; Quaranta, Michela; Vitagliano, Amerigo; Esposito, Federica; Andrisani, Alessandra; Venturella, Roberta; Alviggi, Carlo; Plebani, Mario; Gangemi, Michele; Nardelli, Giovanni Battista; D'Antona, Donato

    2016-04-01

    We conducted an observational cohort study to evaluate whether drugs used for hypothalamic inhibition may impact thyroid function of infertile women scheduled for fresh nondonor in vitro fertilization/intracytoplasmic sperm injection treatment. We considered eligible for inclusion in the study only women with normal thyroid function (serum thyroid-stimulating hormone [TSH] range: 0.2-4.0 mIU/L, serum thyroxin values: 9-22 pmol/L) and negative personal history for previous thyroid disorders. According to which protocols were implemented to gain hypothalamic inhibition, patients were assigned to group A (70 women treated by long gonadotropin-releasing hormone [GnRH] agonist protocol) or to group B (86 women treated by flexible GnRH antagonist protocol). Before initiating controlled ovarian stimulation (COS), both groups were further stratified into 4 subgroups: A1 (46 of the 70 women) and B1 (61 of the 86 women) in women with a baseline TSH value <2.5 mIU/L, whereas those with a baseline value ≥2.5 mIU/L were assigned to groups A2 (24 of the 70 women) and B2 (25 of the 86 women). Prior to initiating stimulation (T-0), 17-β-estradiol (E(2)) and TSH serum values were dosed in all women and repeated on T-5 (day 5 of COS) and subsequently every 2 days until T-ov-ind (ovulation induction day) and T-pick-up (oocytes retrieval day). In case of detection of TSH levels above the cutoff, patients were screened for thyroxin and thyroid autoantibody serum values. In group A, E(2) at T-ov-ind was significantly increased compared to group B (P < .01), whereas TSH values showed an opposite trend (not significantly modified in group A, whereas significantly increased in group B; P < .001). A total of 64 women were found to have TSH values above the cutoff during COS: 7 in group A (11%) and 57 in group B (89%). Among them, 5 (71.4%) of the 7 in group A displayed hypothyroidism (and 4 of the 5 autoantibody positivity), whereas in group B, 6 (10.5%) of the 57 displayed

  7. Reduced levels of GH during GnRH analogue treatment in pubertal short girls born small for gestational age (SGA).

    Science.gov (United States)

    van der Kaay, Daniëlle C M; Rose, Susan R; van Dijk, Marije; Noordam, Cees; van Rheenen, Eva; Hokken-Koelega, Anita C S

    2009-06-01

    Several studies showed a decrease in height velocity during GnRH analogue (GnRHa) treatment. No information is available on GH levels during GnRHa treatment in short SGA girls. To study overnight GH profiles and IGF-I and IGFBP-3 levels in girls with Tanner stage 2 and stage 3, before and after 3 months of GnRHa treatment, and to compare levels with those found in prepubertal short SGA girls. Twenty-four pubertal and 16 prepubertal short SGA girls. After baseline overnight GH profiles, pubertal girls received leuprorelide acetate depots of 3.75 mg subcutaneously every 4 weeks. GH, IGF-I and IGFBP-3 levels. At baseline, GH levels were comparable to levels found in prepubertal short SGA girls and IGF-I and IGFBP-3 SDS were significantly below the population mean. After 3 months of GnRHa treatment, AUC(0) (P = 0.02), mean (P = 0.02) and maximum GH levels (P = 0.008) had significantly decreased. Mean GH levels were significantly lower than in prepubertal short SGA girls (P = 0.03). Eight girls with more than 40% decrease in mean GH levels also had a significantly greater decrease in IGF-I and IGFBP-3 levels. Mean and maximum GH levels at baseline correlated significantly with those after 3 months of GnRHa treatment. Short SGA girls lack the normal increase in GH levels seen in puberty and have reduced IGF-I and IGFBP-3 levels, which might explain their reduced pubertal growth spurt. GnRHa treatment led to a significant reduction in GH levels. Therefore, combining GnRHa treatment with GH treatment might improve adult height of short SGA girls.